Autoimmune kidney disease

Monash researchers have solved a mystery, revealing how certain immune cells work together to instigate autoimmune kidney disease.The study, led by Professor Michael Hickey and Professor Richard Kitching from Monash University's Centre for Inflammatory Diseases. In glomerulonephritis, an immune disease of the kidney, rogue immune cells damage the kidney via a misdirected inflammatory attack.

Special cells called monocytes continuously patrol the glomeruli by crawling within its blood vessels. Monocytes are very good at 'picking up and removing rubbish' and being on the lookout for signs of infection and tissue injury. However in autoimmunity, some immune cells in the circulation are highly reactive to molecules picked up in the kidney.

Patrolling monocytes can display these molecules to the reactive immune cells in the bloodstream, resulting in the rogue cells remaining in the kidney and turning on an unnecessary and damaging inflammatory attack. This autoimmune damage to the kidney can severely impact on the normal function of the kidney, if left untreated.

 This damage occurs while the cells are moving around in the kidney blood vessels. This process, known as intravascular antigen recognition, has never been described before for the key helper T cells that direct and control the immune response.
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Molecular magnet could improve cancer immunotherapy

According to new research in cell, chemicals that attract specialised immune cells toward tumours could be used to develop better immunotherapies for cancer patients Scientists at the Francis Crick Institute have discovered that immune cells called Natural Killer cells accumulate in tumours and release chemicals that attract specialised dendritic cells (cDC1)-white blood cells known for triggering anti-cancer immune responses to the tumour.

Genes associated with Natural Killer cells and cDC1 correlated with cancer patient survival in a dataset of over 2,500 patients with skin, breast, neck and lung cancers. A similar correlation was seen in an independent group of breast cancer patients, with a particularly positive outcome for women with triple negative breast cancer, which typically has a poor prognosis. The findings have given a renewed appreciation of the importance of Natural Killer cells and cDC1 in the immune response against cancer.

The team showed that prostaglandin E2 (PGE2), a molecule produced by some cancer cells, suppresses Natural Killer cell activity and reduces the responsiveness of cDC1 to the chemical attractants. This suggests that blocking PGE2 with aspirin might help boost the effectiveness of immunotherapies by restoring cDC1 levels in tumours. The research reveals more about the way the body's immune system interacts with cancer, exposing one way in which cancer can avoid attack. It highlight the complexity of this relationship and reveal another way in which the immune system can be harnessed to treat cancer.
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Technology for accelerated wound healing

Researchers at Uppsala University and SLU have found a new way of accelerating wound healing. The technology involves using lactic acid bacteria as vectors to produce and deliver a human chemokine on site in the wounds. The research group is the first in the world to have developed the concept for topical use and the technology could turn out to be disruptive to the field of biologic drugs.

Treatment of large and chronic wounds are a high cost burden to the health care system since effective tools to accelerate healing are lacking. Wound care is today limited to mechanical debridement, use of different dressings and significant amounts of antibiotics preventing or treating wound infections. With the aging population, occurrence of chronic diseases such as diabetes and the alarming global spread of antibiotic resistance, a treatment that kick-starts and accelerates wound healing will have a significant impact.

There have been many attempts to solve the problem of chronic wounds that have failed. Drug candidates currently in late stage clinical trials comprise of growth factors, which are traditional protein-based biological drugs associated with high costs, and some trials have been prematurely terminated.

Researcher have developed a drug candidate, a next-generation biologic medical product, and are now publishing the fantastic results from the preclinical part where wound healing was strongly accelerated in mice," says Mia Phillipson, Professor at the Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University.

The acceleration of the healing process occurs due to changes in the microenvironment in the wound, which change the behaviour of specific immune cells. With the newly developed technology, the researchers can increase the level of a chemokine, CXCL12, for a sufficient time period through continuous delivery directly to the wound surface.

Bioavailability of CXCL12 is synergistically increased within the wound as the bacterial produced lactic acid causes a slight pH drop that inhibits degradation. The chemokine, CXCL12, is endogenously upregulated in injured tissue and by increasing the levels further, more immune cells are recruited and are more specialised to heal the wound, which accelerates the whole process.

The potent effect on acceleration of wound healing is demonstrated in healthy mice but also in two models of diabetes, one model of peripheral ischemia as well as in a model using human skin biopsies. There were clear differences in the composition of immune cells in the wounds and the immune cells present produced higher levels of TGFß at earlier time points. The treatment was local without systemic exposure.
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E-cigarettes flavours are toxic

Sugar and spice are not healthy when it comes to vaping or inhalation. Exposure to e-cigarette flavoring chemicals and liquids can cause significant inflammation to monocytes, a type of white blood cell and many flavoring compounds are also toxic, with cinnamon, vanilla and buttery flavors among the worst. That's the finding of new research published in open-access journal
Frontiers in Physiology, which also found that mixing e-cigarette flavors has a much worse effect than exposure to just one.

The use of e-cigarettes has exploded in the past decade as traditional cigarette consumption has declined. Vaping exposes the lungs to flavoring chemicals when the e-liquids are heated and inhaled. Since the flavoring chemicals are considered safe to eat, e-cigarettes are often considered and advertised as a healthier alternative to traditional cigarettes.

This new study, led by researchers at the University of Rochester Medical Centre in the United States, wanted to test the assumption that vaping nicotine-free flavored e-liquids is safer than smoking conventional cigarettes. Previous studies show that flavors used in e-cigarettes cause inflammatory and oxidative stress responses in lung cells.

Users of e-cigarettes also show increased levels oxidative stress markers in the blood compared to non-smokers. The new study extends this to assess the effects of commonly used flavoring chemicals, as well as e-liquids without nicotine, directly on immune cells-a type of white blood cell called monocytes.

Exposure to the e-cigarette flavoring chemicals and e-liquids led to higher production of two well-established biomarkers for inflammation and tissue damage mediated by oxidative stress. Furthermore, many of the flavoring chemicals caused significant cell death with some flavors being more toxic than others.
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How MRSA infection compromises lymphatic function

Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. Massachusetts General Hospital (MGH) investigators describe finding that MRSA infection impairs the ability of lymphatic vessels to pump lymphatic fluid to lymph nodes in mouse models, which may contribute to the frequent recurrences of MRSA infection experienced by patients.

 MRSA produces toxins that kill the muscle cells critical to the pumping of lymph, MRSA with a genetic deficiency that lowers the amount of toxin produced does not kill lymphatic muscle cells, which both supports the role for bacterial toxins in the post-MRSA impairment of lymphatic function and may also suggest a possible treatment strategy. Patients with lymphedema - swelling and fluid buildup caused by damage to or blockage of the lymphatic system - are particularly prone to recurrent infections, which can exacerbate existing lymphedema.

In contrast to the cardiovascular system, in which blood is propelled through arteries and veins by the pumping of the heart, in the lymphatic system, lymphatic fluid - which carries immune cells and other important factors - is pumped along by the contraction of the lymphatic vessels , driven by lymphatic muscle cells. Experiments in mouse models of MRSA tissue infections - conducted by team members including lead author Dennis Jones, PhD - revealed that the infection itself cleared within 30 days and associated inflammation was gone within 60 days.

 The lymphatic vessels in MRSA-infected tissues showed abnormalities - including increased vessel diameter and weaker, less frequent contractions - that were still present 120 days after the induction of infection. Close examination revealed that the number of lymphatic muscle cells surrounding lymphatic vessels was depleted as late as 260 days after infection. Lymph pumping was restored after the resolution of sterile inflammation, MRSA-induced impairment persisted long after the infection was resolved and the inflammation had stopped. This persistence long after bacteria have been cleared can be explained by the loss of lymphatic muscle cells.

Exposure of cultured mouse and human lymphatic or smooth muscle cells to the proteins produced by MRSA led to the death of these cells, and detailed analysis of MRSA-produced proteins identified a significant number of known pathogenic toxins. Since expression of many MRSA toxins is controlled by a genetic element called the accessory gene regulator (agr), the team tested a mutant form of MRSA lacking the agr against several types of cultured cells and in their animal model.

The agr-mutant MRSA did not produce the muscle-cell-killing proteins, and lymphatic function - including the strength and frequency of vessel contraction - was significantly better in mice infected with the mutant strain than in animals infected with a non-mutated strain. Targeting the action of the agr during and after MRSA infection may preserve lymphatic muscle cells and, as a result, lymphatic function.
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Links between stress and sickness

A Michigan State University researcher is providing new insight into how certain types of stress interact with immune cells and can regulate how these cells respond to allergens, ultimately causing physical symptoms and disease. A stress receptor, known as corticotropin-releasing factor, or CRF1, can send signals to certain immune cells, called mast cells, and control how they defend the body.

Mast cells become highly activated in response to stressful situations the body may be experiencing. When this happens, CRF1 tells these cells to release chemical substances that can lead to inflammatory and allergic diseases such as irritable bowel syndrome, asthma, life-threatening food allergies and autoimmune disorders such as lupus.

One chemical substance, histamine, is known to help the body get rid of invading allergens such as pollen, dust mites or the protein of a particular food like a peanut or shellfish. The histamine causes an allergic reaction and in a normal response, helps the body clear the allergen from its system.
If a patient has a severe allergy or is under a lot of stress, then this same response can be amplified, resulting in more severe symptoms ranging from trouble breathing, anaphylactic shock or death.

Researchers compared the histamine responses of mice to two types of stress conditions - psychological and allergic - where the immune system becomes overworked. One group of mice was considered "normal" with CRF1 receptors on their mast cells and the other group had cells that lacked CRF1. While the 'normal' mice exposed to stress exhibited high histamine levels and disease, the mice without CRF1 had low histamine levels, less disease and were protected against both types of stress. This shows that CRF1 is critically involved in some diseases initiated by these stressors.

The CRF1-deficient mice exposed to allergic stress had a 54 percent reduction in disease, while those mice who experienced psychological stress had a 63 percent decrease. The results could change the way everyday disorders such as asthma and the debilitating gastrointestinal symptoms of irritable bowel syndrome are treated.
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Effects of estrogen treatment in multiple sclerosis

A study by UCLA researchers reveals the cellular basis for how the hormone estrogen protects against damage to the central nervous system in people with multiple sclerosis (MS). The researchers found that estrogen treatment exerts positive effects on two types of cells during disease -immune cells in the brain and also cells called oligodendrocytes. Complementary actions on these two types provide protection from disease.

Multiple sclerosis is a chronic autoimmune, neurodegenerative disease marked by visual impairment, weakness and sensory loss, as well as cognitive decline. These symptoms emerge when inflammatory immune cells destroy the myelin sheath that surrounds nerve processes called axons. Loss of that protective insulation disrupts electrical communication between nerve cells. The third trimester of pregnancy has been previously shown to reduce relapse rates by approximately 70 percent as compared to before pregnancy, and other studies have shown benefit over the long term due to multiple pregnancies.

An estrogen unique to pregnancy that is made by the fetus and placenta has been proposed by Dr. Rhonda Voskuhl and colleagues to mediate this pregnancy protection in both the MS mouse model as well as in two successfully completed clinical trials of estriol treatment in MS patients. How that happens has remained a critical question. Voskuhl, who led the latest study, reported mouse studies showing that estrogen protected the brain from damage by activating a protein called estrogen receptor beta (ERb). Her new research identifies which cells within the brain are mediating this protective effect.

The researchers first genetically eliminated ERb in either immune cells of the brain or in oligodendrocytes, the cells that make the myelin sheath, as a way of making cells unresponsive to estrogen during the MS like disease in mice. They then treated mice without or with ERb in these cells to ask if disease protection was lost or not. Loss of protection during treatment meant that the treatment was acting on the cell that had the receptor removed. Results showed that the estrogen-like treatment was acting on both immune cells of the brain as well as on oligodendrocytes, together resulting in repair of myelin and less disability.

Drug developers often optimize therapies by targeting only one single cell type. By contrast, this study confirms that this estrogen-like compound can combat MS via complementary effects on two distinct cell types. Voskuhl and other UCLA researchers are in fact now developing a next-generation estrogen-like compound with robust biochemical effects on oligodendrocytes and immune cells in the brain.
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Antibiotics may reduce the ability of immune cells

Antibiotics normally act in concert with an organism's immune system to eliminate an infection. However, the drugs can have broad side effects, including eliminating "good" bacteria in the course of fighting off a pathogen. Researchers has shown that antibiotics can also reduce the ability of mouse immune cells to kill bacteria, and that changes to the biochemical environment directly elicited by treatment can protect the bacterial pathogen.

Different types of antibiotics can damage mitochondria in mice and in human epithelial cells, and that bacterial susceptibility to drugs can be affected by small molecules, called metabolites, released by cells as intermediates of their metabolic reactions. Antibiotic treatment might further alter the infection microenvironment in ways that impact bacteria and immune cells.

To investigate, the team treated mice infected by Escherichia coli bacteria with a commonly used antibiotic called ciprofloxacin, administered through the animals' drinking water at concentrations relative to what a human would receive, and quantified the biochemical changes. The researchers found that the antibiotic treatment elicited systemic changes in metabolites-not by influencing the microbiome, but by acting directly on the mouse tissues.

On further investigation, the team determined that metabolites released by mouse cells made E. coli more resistant to ciprofloxacin. Antibiotic exposure also impaired immune function by inhibiting respiratory activity in immune cells: Macrophages treated with ciprofloxacin were less able to engulf and kill E. coli bacteria.
The results highlight the potential of antibiotics to modulate the immune system, and reveal the importance of the metabolic microenvironment in resolving an infection.
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Vitamin D may prevents Rheumatoid arthritis

Maintaining sufficient vitamin D levels may prevent the onset of inflammatory diseases like rheumatoid arthritis, it is less effective once inflammatory disease is established because diseases such as rheumatoid arthritis leads to vitamin D insensitivity. The impact of vitamin D on inflammatory disease cannot be predicted using cells from healthy individuals or even from the blood of patients with inflammation as cells from the disease tissue are different.

If vitamin D is to be used in patients with rheumatoid arthritis, clinicians may need to prescribe much higher doses than currently provide a treatment that also corrects the vitamin D insensitivity of immune cells within the joint. Vitamin D is a potent modulator of the immune system. In particular, vitamin D can suppress inflammation in autoimmune diseases such as rheumatoid arthritis. Patients with rheumatoid arthritis are frequently vitamin D deficient and may receive vitamin D supplementation.

The study involved using paired peripheral blood and synovial fluid from the inflamed joint of patients with rheumatoid arthritis. The current understanding of vitamin D and rheumatoid arthritis is based on studies of patient blood which may not truly represent the situation at the site of inflammation -the joints. Investigating responses to the active form of vitamin D in immune cells from the inflamed joints of patients with rheumatoid arthritis compared to blood from the same patients, the inflamed joint immune cells were much less sensitive to active vitamin D.

This occurred because immune cells from the joints of rheumatoid arthritis patients are more committed to inflammation, and therefore less likely to change, even when they respond to vitamin D. Maintaining sufficient vitamin D may prevent the onset of inflammatory diseases like rheumatoid arthritis. However, for patients who already have rheumatoid arthritis, providing vitamin D might not be enough. Instead much higher doses of vitamin D may be needed, or possibly a new treatment that corrects the vitamin D insensitivity of immune cells within the joint.
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Breastmilk prevents food allergy

A mother's diet can protect nursing newborns against food allergies. In mice, milk from mothers exposed to egg protein gave protection against egg allergy to the mothers and offspring, but also to fostered newborns whose birth mothers had not received egg. Newborns gained an insignificant degree of protection from mothers who were exposed to egg during pregnancy but did not breastfeed them. The protective effect was strongest when the newborns were born to and nursed by mothers who were exposed to egg before and during pregnancy and breastfeeding.

 Pregnant and breastfeeding mothers were sometimes cautioned against consuming foods that commonly cause allergy, such as milk, egg, peanut, tree nuts, soy, wheat, fish and shellfish. More recently, feeding peanut foods to infants at high risk for peanut allergy was shown to decrease, not increase, the babies' likelihood of developing allergy to peanut. Allergists now recommend that, unless mothers already have diagnosed food allergies, they should not avoid allergenic foods while pregnant and nursing. Mothers are free to eat a healthy and diverse diet throughout pregnancy and while breastfeeding. Eating a range of nutritious foods during pregnancy and breastfeeding will not promote food allergies in developing babies, and may protect them from food allergy.

Maternal and early childhood diets do not cause food allergies in children. Most children do not develop food allergies, regardless of how they are fed., while some children develop allergies even when fed an optimal diet. The food allergy protections described in the study are dependent on specific proteins, some provided by the mother, others by the offspring. By identifying these proteins and proposing a mechanism through which mother and offspring contribute to the development of food tolerance in the newborn mouse, the research opens new opportunities to study how the protections break down in the case of food allergy and how such breakdowns might be prevented.

Preventing food allergy is critical because there are no approved treatments for this serious and potentially life-threatening condition. The mouse study found that when a nursing mother is exposed to a food protein, her milk contains complexes of the food protein combined with her antibodies, which are transferred to the offspring through breastfeeding. Aided by a protein in the offspring's gut lining and some immune cells, the food protein-antibody complexes are taken up and introduced to the offspring's developing immune system, triggering the production of protective cells that suppress allergic reactions to the food. These protective cells persist after antibodies from the mother are gone, promoting long-term tolerance to the food. A similar mechanism may offer protection to human infants.
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The secrets of Ebola

In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone. Conducting a sweeping analysis of everything from enzymes to lipids to immune-system-associated molecules, the teamfound 11 biomarkers that distinguish fatal infections from nonfatal ones and two that, when screened for early symptom onset, accurately predict which patients are likely to die.

Health workers collected blood samples from patients after they were diagnosed with Ebola and at multiple points thereafter.They obtained 29 blood samples from 11 patients who ultimately survived and nine blood samples from nine patients who died from the virus. For comparison, the research team also obtained blood samples from 10 healthy volunteers with no exposure to Ebola virus.
"Our team studied thousands of molecular clues in each of these samples, sifting through extensive data on the activity of genes, proteins and other molecules to identify those of most interest.

The team found that survivors had higher levels of some immune-related molecules, and lower levels of others compared to those who died. Plasma cytokines, which are involved in immunity and stress response, were higher in the blood of people who perished. Fatal cases had unique metabolic responses compared to survivors, higher levels of virus, changes to plasma lipids involved in
processes like blood coagulation, and more pronounced activation of some types of immune cells.

Pancreatic enzymes also leaked into the blood of patients who died, suggesting that damage from these enzymes contributes to the tissue damage characteristic of fatal Ebola virus disease. The study showed that levels of two biomarkers, known as L-threonine (an amino acid) and vitamin D binding protein, may accurately predict which patients live and which die. Both were present at lower levels at the time of admission in the patients who ultimately perished.

When Ebola virus leads to death, experts believe it is because of overwhelming viral replication. Symptoms of infection include severe hemorrhaging, vomiting and diarrhea, fever and more. In the current Ebola study, the team found that many of the molecular signals present in the
blood of sick, infected patients overlap with sepsis, a condition in which the body in response to infection by bacteria or other pathogens mounts a damaging inflammatory reaction.
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Immune cells can repair damaged nerves

Immune cells fight infections, in a new study, scientists have discovered how they also help the nervous system remove debris, clearing the way for nerve regeneration after injury. Some immune cells- neutrophils can clean up nerve debris. Neutrophils are one of the most common types of immune cells and known to engulf microorganisms, but they are not associated with peripheral nerve damage caused by diabetes or trauma.

Damaged nerve cells produce a stream of molecular lures that specifically attract neutrophils to injury sites in mice. Damaged mouse sciatic nerves produced hundreds of times the normal amount of two "chemoattractant" molecules, Cxcl1 and Cxcl2, which attach to the surfaces of neutrophils and draw the immune cells into injured tissue.

Once at the injury site, the neutrophils engulf cellular debris caused by the nerve damage, tidying up the area so the cells can repair themselves. Without the cellular clearance mechanism, nerves can't properly regenerate after injury. The experiments included sorting immune cells found at injury sites by molecules on their cellular surfaces, and many hours looking at mouse cells through the microscope.

Several different cells pick up the slack in the absence of macrophages, it was the neutrophil that emerged as a major contributor to debris removal. We also discovered that when we depleted neutrophils, nerve debris clearance was significantly halted in both normal mice and mice lacking a major population of macrophages.

Without neutrophils, nerve cells could not properly clear debris. This could leads to new therapeutics designed to repair nerve cells damaged by neurodegenerative disease. The clearance of debris after an injury is necessary for effective nerve regeneration. Immunostimulant molecules that target neutrophils at nerve injury location might enhance clean-up and promote nerve cell repair. Immunostimulant molecules are used to treat chronic infections and immunodeficiency.
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Activation of immune T cells changes behavior

Researchers have discovered that T cells immune cells that protect the body from infections and cancer change the body's metabolism when they are activated, and that this activation leads to changes in behavior.

It is currently known that individual T cells change their metabolism to meet their energy needs after being activated, but the systemic metabolic effect of sustained activation of the immune system has remained unexplored.

 To understand the systemic effects, the group looked at T cell activation in mice designed to lack a surface receptor called PD-1, which is necessary for inhibiting the activity of T cells. T cells remain activated in mice without the receptor, similar to those in the immune systems of people with certain types of autoimmune disease.

In these mice, they found that amino acids molecules that are used to build proteins were depleted in the blood, and that they were increased in the T cells themselves, implicating the T cells in the change. The team tracked and imaged amino acids in many organs, and found that the depletion of amino acids from the blood was taking place due to the accumulation of amino acids in activated T cells in the lymph nodes, showing that strong or long lasting immune responses can cause metabolic changes elsewhere in the body.

Researchers analyzed the biochemistry of the brain, they found that the systemic decrease in the amino acids tryptophan and tyrosine in blood led to lower amounts available in the brain, limiting production of the neurotransmitters serotonin and dopamine. These neurotransmitters affect emotions, motivation and fear.

Serotonin is often a target of drugs that combat depression. The researchers found that their depletion in mice without PD-1 resulted in behavioral changes dominated by anxiety and exacerbated fear responses, which could be remedied by providing a diet rich in an essential amino acid.
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How hepatitis C hides in the body

The Hepatitis C (HCV) virus is invisible to the immune system by breaking down communication between the immune cells, it builds virus factories that multiply easily. It takes one to three months from infection to disease, it can lead to liver failure and death. Hepatitis C virus is transmitted through blood and infects the cells in the liver, it is difficult to detect because it does not have symptoms when you get infected.

The virus causes chronic infection that lasts a lifetime. It may take decades before the infection leads to liver failure or cancer, so a lot of people are unaware that they have the virus in their body. They only notice it when they get seriously ill, which may be too late for the treatments that are available. Hepatitis C virus destroys important proteins in the immune system to promote its own growth. The ability to directly manipulate their host cells is the reason some viruses are very harmful to human.

Human cells have a complex inner structure that is divided into different areas, with different sacs that are formed from fatty membranes. Viruses that have the same genetic material as HCV (positively polarized single-stranded RNA) cause major changes in these membrane sacs.

Liver cells infected with HCV had altered membrane sacs. To study whether the IRGM protein caused the changes, researchers employed the CRISPR-Cas system, a technique that is used for regulating cells, in this case to turn off the IRGM protein in the liver cells. When the IRGM is removed from the liver cells, the virus is unable to grow.

The reason for this is that the hepatitis C virus utilizes some of the cells, called the Golgi apparatus, where the protein IRGM has an important function. The Golgi apparatus is a kind of transport centre in the cells. It packs proteins into small sacs called vesicles and sends them where they need to go within the cell, or out to other cells.

The hepatitis C virus utilizes this to build its virus factories by taking over and redirecting these vesicles with the necessary building blocks to the site where the factories are being built. These vesicles are rich in lipids that the virus is entirely dependent on to anchor its factory construction.

When this protein is removed, the virus is no longer able to infiltrate the Golgi apparatus and thus it can't build up its secret network of virus factories. Hepatitis C is transmitted via the blood. Infection is spread primarily through unclean syringes, non-sterilized medical devices, or unsafe blood transfusions.
HVC can also be passed on from mother to child, and through bodily fluids.
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Links between cholesterol and breast cancer

High cholesterol levels have been associated with breast cancer spreading to other parts of the body, researchers discovered that the byproduct of cholesterol metabolism that acts on specific immune cells so that they facilitate the cancer's spread instead of stopping it is responsible for the spread.

Many women will experience metastatic breast cancer, when the breast cancer has spread to other organs, and at that point, there is no effective therapies.

Researchers fed mice with breast cancer tumors a diet high in cholesterol. They confirmed that high levels of cholesterol increased tumor growth and metastasis, and that mice treated with statins cholesterol lowering drugs had less metastasis.

Human body's immune system has the capacity to attack cancer but the cholesterol metabolite hydroxycholestrol 27HC works on immune cells and prevents them from attacking cancer because 27HC acts through the immune system, and not on the breast cancer.
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Immune cells hinder metabolism in adult

Older people do not burn the energy stored in fat cells as efficiently as younger people, this leads to the accumulation of harmful belly fat. The underlying cause for this unresponsiveness in fat cells was unknown.

Researchers discovered a new type of macrophage that resides on the nerves in belly fat. These nerve-associated macrophages become inflamed with age and do not allow the neurotransmitters, which are chemical messengers, to function properly.
The researchers also isolated the immune cells from fat tissue of young and old mice, and then sequenced the genome to understand the problem.

They discovered that the aged macrophages can break down the neurotransmitters called catecholamines, and thus do not allow fat cells to supply the fuel when needed. Lowering a specific receptor that controls inflammation, the NLRP3 inflammasome, in aged macrophages, the catecholamines could act to induce fat breakdown, similar to that of young mice.

Researchers blocked an enzyme that is increased in aged macrophages, restoring normal fat metabolism in older mice, monoamine oxidase and MAOA, is prevented by existing drugs in the treatment of depression. When immune cell interact with nerves and fat cells to reduce belly fat, this enhance metabolism, improve performance and belly fat loss in older people.
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HIV vaccine breakthrough

Vaccines work by imitating an infection and setting up a memory B-cell response in advance of an actual infection. In HIV infection, the body mounts a very strong antibody response in the first few weeks that partially works, reducing the viral load from millions to thousands. However it does not control viral replication any further or eliminate HIV infection, and eventually weakens so that the viral load increases again

An effective HIV vaccine may be a short step away, scientists have overcome a major stumbling block hindering its development. The inability to generate immune cells that stay in circulation long enough to stop the virus from spreading is a big problem in providing cure for HIV.

The problem can be solved  by unblocking a process linked to an HIV protein that was preventing the production of antibody-generating B-cells from the immune system. For a vaccine to work, its effects need to be long lasting, improving B-cell responses to an HIV vaccine is the key to HIV cure. The new method produced desired immune system responses that lasted more than a year in the laboratory experiment.

Producing vaccines that stimulate long-lasting B-cell responses against HIV is the solution to HIV treatment. B-cells need time to make highly effective neutralising antibodies, but in previous studies B-cell responses were so short lived, they disappeared before they had the time to make all the changes necessary to kill HIV.
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Bone marrow protein may be used for stem cell transplant

Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells become after bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells.

Del-1 is a protein that plays a role in gum disease, it regulate the production of blood cells. Targeting it could be an effective way to improve stem cell transplants for both donors and recipients. Modulate levels of Del-1 in patients with certain blood cancers can enhance immune cell production.

Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, it could be a target in many potential applications.

The researchers' investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts.

Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.

In bone marrow transplant experiments, researchers discovered that the presence of Del-1 in recipient
bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.

When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.

The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation.

Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly. People undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.
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DNA sensor and cancer immunotherapy

Tumors stressed by cancer immunotherapy release their mitochondrial DNA into the closer immune cells, causing a host alert system. The chemical alert through the molecule cGAS is an important immune-system sensor for DNA that is in the interior of cells, the cytosol, where DNA should not exist. 

 cGAS connected the innate immune system, which senses initial threats; and the adaptive immune system, which amplifies the anti-tumor response after getting the alert from the innate immune system. The adaptive system battles recurring threats from pathogens. Checkpoints are molecular barriers that cancer cells produce to make themselves undetectable to the immune system. The plan of immunotherapy is to make the cancers detectable.

Current immune checkpoint blockade therapy has been life-extending for many people. The drug targets CD47, a cell surface protein highly expressed in some tumor cells. CD47 signal to block immune cells from killing the cancer cells. cGAS as an innate immune sensor of DNA led to speculation that inhibition of cytosolic DNA sensing could represent a strategy tumor cells used to evade the immune system.

CD47 is found in every cell of the body, and it has long been known that many kinds of cancer cells produce higher amounts of CD47 than healthy cells. CD47 signal helps cancer cells evade detection from the immune system's killer T-cells.

The higher the levels of CD47 found in tumors, the poorer the prognosis for many cancers. Using mouse cells,
the researchers discovered that when cancer cells are stressed by an experimental anti-CD47 immunotherapy, it leaks DNA into nearby dendritic cells, which present antigens to killer T-cells and are considered a bridge between the innate and adaptive immune systems.

 The DNA sensor cGAS sounds the alarm inside those dendritic cells, setting off a signaling cascade that alerts the
immune system and unleashes the cancer-killing T-cells. cGAS is essential for cancer immunotherapy by immune checkpoint blockade. Activating DNA comes from the mitochondria of the cancer cells. Tumor-originated mtDNA was recognized by the DNA sensor cGAS in dendritic cells during anti-CD47 treatment.

 cGAS-STING-IRF3 signaling pathway plays a critical role to drive robust innate and adaptive immune response upon anti-CD47 therapy. Understanding this mechanism of anti-CD47 therapy may make it possible to design new combination strategies to improve current immune checkpoint blockade therapies by modulating the innate sensing of mtDNA.
       

Fatty liver can damage other organs

Nonalcoholic fatty liver disease  NAFL increases the risk of chronic liver diseases such as liver cirrhosis, liver cancer, type 2 diabetes and cardiovascular diseases. Altered secretion of the fatty liver increases production of glucose, fats, and proteins like hepatokine fetuin-A, which are releases into the bloodstream.

The secreted substances of the fatty liver enter other organs and trigger further reactions. People who had experienced an increased pancreatic fatty degeneration have reduced insulin secretion.

Fatty liver and fatty degeneration of the pancreas triggers increased local immune cell infiltration and inflammation that increase the disease.
However, adipose tissue is not harmful, it can even have protective effects: adipose tissue located around the blood vessels of the kidney has regenerative properties.

The factor that leads to pathological changes is fetuin-A, which is produced by the fatty liver, instead of protecting tissue as before, the adipose tissue brings out inflammatory processes that leads to a restriction of renal function.
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