Vagus nerve stimulation may reduce the symptoms of rheumatoid arthritis

 Electrostimulation of the vagus nerve may be key to reducing the symptoms of rheumatoid arthritis, according to findings that scientists presented at the Annual European Congress of Rheumatology in Madrid, Spain.

This research gives hope that there may be a new way to help treat this autoimmune condition.

The vagus nerve, which is a very long nerve that runs between the brain and the neck, chest, and abdomen, is a complex structure.

Previous research has found an inflammatory reflex in the vagus nerve that reduces the production of cytokines, including certain molecules that are a component of autoimmune conditions. These molecules are called tumor necrosis factor (TNF).

The immune systems of healthy people block TNF, but in those with certain autoimmune conditions, excess TNF makes its way into the bloodstream and causes inflammation and a higher rate of symptoms associated with the conditions.

TNF is a target in many rheumatoid arthritis (RA) drugs, such as infliximab (Remicade) or etanercept (Enbrel). Many people call these drugs TNF-blockers.

The researchers thought that if they could boost this naturally occurring reflex in the vagus nerve, it might have a similar result — or one that was even better, as drugs that aim for TNF also suppress the immune system and have other unwelcome side effects.

“This is a really exciting development,” says Prof. Thomas Dörner, Chairperson of the Scientific Programme Committee at the Annual European Congress of Rheumatology, which this year takes place in Madrid, Spain.

“For many [people living with] RA, current treatments don’t work, or aren’t tolerated. These results open the door to a novel approach to treating not only RA but other chronic inflammatory diseases. This is certainly an area for further study,” adds Prof. Dörner.

Small neurostimulator led to big findings

The researchers implanted a small neurostimulator, called a MicrioRegulator, into 14 people with RA. To qualify for the study, each person had tried at least two medications that worked in different ways but that hadn’t helped reduce their symptoms.

The scientists then divided the participants into three groups: a placebo group, a group that had vagus stimulation once per day, and a group that had vagus stimulation four times per day.

The study, which took place over 12 weeks, revealed that those in the once-per-day group had a much better result, symptom-wise, than those in the other two groups — including those that had stimulation four times each day.

Both stimulation groups also had a distinct reduction of more than 30% in their cytokine levels during the course of the study.

How RA affects people

Unlike osteoarthritis, which occurs when cartilage in the joints breaks down over time, RA can develop at any age. That said, it is more likely to affect people ages 30–60.

In the United States, there are around 1.5 million people with the condition, and it tends to affect around three times as many women than men.

In those with RA, the body’s immune system is overactive and attacks healthy tissue in the body — in this case, the lining of the joints.

Over time, this inflammation can damage cartilage and the bones themselves, with joint spacing becoming more narrow. This results in a loss of mobility and flexibility. Once the damage has set in, it is irreversible; so, the goal is to identify the condition early and treat it aggressively.

Symptoms can vary from person to person, but early symptoms tend to include joint pain or swelling that lasts for 6 weeks or longer, stiffness in the morning that lasts for at least 30 minutes, or both.

RA tends to affect more than one joint, and it also affects smaller joints in the hands, feet, and wrists more often than it does larger joints. Also, RA is often symmetrical and affects joints on both sides of the body.

What does the future hold?

Although surgically implanting small neurostimulators into every person with RA is probably not feasible, reasonable, or required, this study does shine a light on potential therapy that can help those who do not respond well to traditional medications for the condition.

The findings of this research will also pave the way for future studies.

“Our pilot study suggests this novel MicroRegulator device is well tolerated and reduces signs and symptoms of [RA],” says Dr. Mark Genovese, the James W. Raitt Endowed Professor of Medicine at Stanford University in California.

Source - Medical News Today

Stem cell therapy for rheumatoid arthritis

 Rheumatoid arthritis is an autoimmune condition that mainly affects the joints. Stem cell therapy is a relatively new area of research that is showing promise in treating autoimmune conditions such as this.

In rheumatoid arthritis (RA), the immune system mistakenly attacks the tissue that lines the joints, which can cause pain, inflammation, swelling, and stiffness.

This inflammation can extend to the cartilage that covers the ends of joints and cause irreversible damage and loss of function. It can also damage other tissues, including the lungs, heart, kidney, skin, and eyes.

Stem cell therapy may help reduce inflammation and increase the presence of healthy cells in the body. This article outlines the current knowledge on stem cell therapy as a possible treatment for RA.

What is stem cell therapy?

A stem cell is a type of cell not specialized to perform a specific role. Instead, it has the unique ability to develop into one of many different types of cell.

Stem cell therapy uses stem cells to replace dead and diseased cells within the body.

The human body contains over 200 different types of cell. Usually, each type has certain characteristics that allow it to perform a specific role.

Cells with similar roles group together to form tissues, which then organize to form the body’s organs. For example, the heart is a collection of muscle tissues.

Scientists source the stem cells from body tissue, either from an embryo or an adult human, and isolate them in the laboratory. After manipulating the cells to develop into specific types, they then inject the cells into the recipient’s blood or tissue.

How can it help treat RA?

Researchers are investigating ways of using stem cells to control inflammation and regenerate damaged tissues.

RA causes inflammation in the tissues between joints. This results in a loss of cartilage, which is the connective tissue that cushions the joints. Over time, cartilage loss can damage the joint and nearby bone.

Mesenchymal stem cells (MSCs) are types of stem cell that can develop into cartilage and bone. Synovial MSC therapy involves injecting these cells directly into the tissues surrounding the affected joints.

Some researchTrusted Source shows that MSCs are also able to suppress the immune system and reduce the body’s inflammatory response. This makes MSC therapy a promising treatment option for autoimmune conditions such as RA.

Although some clinics use stem cell therapy to treat arthritis, it is not standard practice and may have some serious side effects. Stem cell research is still in the very early stages of scientific investigation and needs more analysis.

What the research says

One 2013 study investigated the efficacy of MSC therapy for people with RA.

All 172 participants continued to take their regular RA medication during the course of the study. A subset of the participants also received two MSC treatments via intravenous injection, while another subset received placebo injections (the controls).

Compared with the controls, those who received the MSC treatment showed a significant remission of the condition. The team measured the extent of remission using the improvement criteria of the American College of Rheumatology, the 28-joint disease activity score, and the Health Assessment Questionnaire.

Improvements also correlated with increased levels of regulatory T cells (RTCs) in the blood. RTCs stop the immune system from attacking the body’s own cells. As such, they play a vital role in controlling inflammation.

One 2015 studyTrusted Source reported similar effects of MSCs on the immune cells of mice with RA.

Its authors explain that MSC treatment increased RCT levels while lowering levels of cells that promote inflammation.

The Food and Drug Administration (FDA)Trusted Source state that clinical trials of MSC therapy for inflammatory conditions have not produced consistent results.

Until recently, researchers sourced human MSCs (hMSCs) from a range of tissues and donors. These different cell batches can vary greatly in their ability to suppress the immune system.

In 2017, scientists began developing reliable methods for predicting the efficacy of different batches of hMSCs. Conducting further research using these methods may help scientists determine whether stem cell therapy can help treat RA.

FDA regulation

Currently, the FDATrusted Source only approve the use of umbilical hematopoietic stem cells (uHSCs).

These cells derive from umbilical cords and can develop into different types of blood cell. People mainly receive uHSCs to help treat blood disorders.

The FDA do not regulateTrusted Source the use of other types of stem cell, such as MSCs. However, they may approve and oversee clinical trials that use such cells.

Clinical trials take place under an FDA-permitted Investigational New Drug Application, which indicates that the trial meets their safety standards.

Risks and side effects

Stem cell therapy can cause some health complications.

Such complications are likely to be much more common than official figures suggest, however, as unregulated clinics that provide these treatments do not need to report adverse health effects in their patients.

Examples of complications that can arise from stem cell treatments include:

Infection

Any time a cell leaves the body, it can become contaminated with viruses and bacteria.

When a healthcare professional injects these cells into a person’s body, these pathogens can cause the person to become sick.

Even cells that come from the recipient’s own body can cause an infection or spread an existing infection.

Exacerbation of RA

According to one 2014 review, the use of synovial MSCs to treat arthritic joints has the potential to worsen RA.

Injecting MSCs directly into joint tissue triggers the development of synovial fibroblasts. These are cells that play a role in joint inflammation and destruction.

Cancer

The authors of that same 2014 review note that intravenous administration of MSCs could suppress the immune response, which protects against cancerous cells.

This could allow cancerous growths to manifest more easily.

Potential long-term risks

Most stem cell research is still in the early stages of clinical trials, so scientists are unsure of the potential long-term risks of this type of therapy.

According to the FDA, further clinical trials are necessary to establish whether — and to what extent — the benefits of stem cell treatments outweigh the risks.

Considerations

The International Society for Stem Cell Research offer the following advice for people considering stem cell treatments:

• Avoid clinics that offer unregulated treatments.
• Avoid treatments that have not undergone successful clinical trials.
• Avoid participating in research that is not part of an FDA-approved clinical trial.
• Talk to a doctor or rheumatologist about the potential risks of stem cell therapy.
• Beware of clinics that downplay the risks associated with their treatments.
• Beware of clinics that use patient testimonials and persuasive language in place of scientific evidence.

Summary

Stem cell therapy is still a relatively new area of research. However, early trials suggest that such therapies may be effective against a range of autoimmune conditions, including RA.

MSCs are one type of stem cell that seems to show promise for the treatment of RA. Studies show that these cells can suppress immune system overactivity, which helps control chronic inflammation.

However, the FDA do not currently regulate the use of stem cells as a treatment for RA. Scientists have conducted too few studies to confirm that such treatments are safe or effective.

People should be wary of clinics that offer these treatments. It is also best to speak to a doctor or rheumatologist before starting a new treatment.

Those who wish to take part in a clinical trial should check to make sure that it is FDA-approved.

Source - Medical News Today

Common arthritis treatment JAK inhibitors are effective, study finds

 

• Researchers compared the efficacy and safety of four JAK inhibitors, a medication used to treat rheumatoid arthritis (RA).
• According to the researchers, no significant differences in efficacy or safety were observed between the four medications.
• Over 85% of participants remained on the medication during the six-month trial.

Rheumatoid arthritis is an autoimmune and inflammatory disease, according to the Centers for Disease Control and Prevention (CDC)Trusted Source. Immune cells attack healthy tissue by mistake, usually in the joint’s lining, causing inflammation.

Typically, joints in the hands, wrists, and knees are affected. It can cause chronic pain, instability, and deformity. RA can also affect organs like the lungs, heart, and eyes.

Available biological disease-modifying medications (bDMARDs) effectively reduce disease activity and achieve remission. However, patients receive these via IV or subcutaneous injection.

JAK inhibitors are another type of RA medication that can be taken orally. They can also delay the progression of the disease.

Typically, treatment for RA starts with conventional DMARDs. If the response is not satisfactory, bDMARDs or JAK inhibitors might be recommended, according to a 2022 review.

These medications are more specific at targeting inflammatory markers and more efficient at inducing remission and low disease activity.

In a new study published on November 1 in Rheumatology, researchers in Japan completed a retrospective study comparing the efficacy and safety of four JAK inhibitors for treating rheumatoid arthritis (RA):

• tofacitinib (TOFA)
• baricitinib (BARI)
• peficitinib (PEF)
• upadacitinib (UPA)

The researchers determined no significant difference in efficacy or safety between the four JAK inhibitors they evaluated.

Study co-author Dr. Shinya Hayashi of the Department of Orthopedic Surgery at Kobe University Graduate School of Medicine, Japan, told Medical News Today:

“Several papers demonstrated the efficacy and safety of difference among JAK inhibitors,” However, those reports did not adjust patients’ backgrounds. We first compared the efficacy of JAK inhibitors after patients background matching. The efficacy and safety of TOF, BAR, PEF, and UPA were not significantly different for the treatment of RA patients.”

 What do JAK inhibitors do for rheumatoid arthritis?

There were 622 patients treated at seven major university hospitals in Japan. They were treated with JAK inhibitors and monitored for side effects, disease improvement, and whether they wanted to continue taking the medications.

The researchers used the Clinical Disease Activity Index, C-reactive protein value, and modified Health Assessment Questionnaire to measure the effectiveness of the medications after six months of use.

According to a media release, the researchers found that roughly 1 in 3 RA patients reached remission, with 3 in 4 reaching low disease activity.

The researchers noted that after six months, over 80% of the subjects were still on JAK inhibitor drugs. Retention rates over six months included:

• Overall – 85.4%
• TOFA – 87.4%
• BARI – 89.5%
• PEF – 82.8%
• UPA – 83%.

“Medical professionals can feel comfortable choosing JAK inhibitors if a patient failed bDMARD treatment,” Dr. Hayashi noted.

What are the side effects of JAK inhibitors?

A small number of adverse events among patients using JAK inhibitors to treat RA were reported.

To that end, the FDA’s black box warningTrusted Source on JAK inhibitors indicates several health risks, including an increased risk of cardiovascular events. These include:

• bacterial, viral, and fungal infections
• opportunistic infections, such as tuberculosis
• higher rate of lymphoma, lung cancer, thrombosis, pulmonary embolism, venous, and arterial thrombosis

Individual JAK inhibitors could have additional side effects.

More research in the broader RA population needed

Although the study had some notable strengths, such as using real-world settings rather than controlled trials to determine the effectiveness and safety of JAK inhibitors, it did have some limitations.

First, the researchers did not closely examine the link between side effects and discontinuation of the medication.

In addition, due to the small number of participants, the researchers could not generalize the results to the larger RA population.

The observational duration was only 24 weeks, and more studies with longer durations are needed.

Lastly, the scientists did not monitor changes in dosage during the study period.

What lifestyle changes can help with rheumatoid arthritis?

Chronic pain associated with RA can affect people in many ways — personally, socially, and economically.

According to a 2022 reportTrusted Source, certain lifestyle factors are associated with chronic pain severity, such as:

• physical inactivity
• stress
• poor sleep
• unhealthy diet
• smoking

Dr. Klee Bethel, director of Interventional Pain Management and Regenerative Medicine at Sonoran University, told MNT that gentle exercises best suit people with RA.

Dr. Bethel recommended the following gentle exercises for RA:

• walking
• dancing
• yoga
• tai chi

If you live with RA and experience discomfort with any form of movement, ask your doctor for guidance about exercises that best suit your needs.

Source - Medical News Today

Could the nerve cells that scratch be the solution for itch?

 It can be a relief to scratch the occasional itch, but when itch gets out of control, it can become a serious health problem. How does the body know when to stop?

Scientists at UC San Francisco are getting close to an answer. In a breakthrough that could transform how doctors treat conditions from eczema to allergies, they have discovered a feedback loop centered on a single immune protein called IL-31 that both causes the urge to itch and dials back nearby inflammation.

The findings, published on October 13th in Science Immunology, lay the groundwork for a new generation of drugs that interact more intelligently with the body's innate ability to self-regulate.

Previous approaches suggested that IL-31 signals itch and promotes skin inflammation. But the UCSF team discovered that nerve cells, or neurons, that respond to IL-31, triggering a scratch, also prevent immune cells from overreacting and causing more widespread irritation.

"We tend to think that immune proteins like IL-31 help immune cells talk to one another, but here, when IL-31 talks to neurons, the neurons talk right back," said Marlys Fassett, M.D., Ph.D., UCSF professor of dermatology and lead author of the study. "It's the first time we've seen the nervous system directly tamp down an allergic response."

The discovery could eventually change how asthma, Crohn's and other inflammatory diseases are treated, due to IL-31's presence throughout the body.

"IL-31 causes itch in the skin, but it's also in the lung and in the gut," said Mark Ansel, Ph.D., UCSF professor of immunology and senior author of the study. "We now have a new lead for fighting the many diseases involving both the immune and nervous systems."

More than an itch

IL-31 is one of several "itch cytokines" because of its ability to instigate itch in animals and people. Fassett, a dermatologist and a researcher, has wanted to know why since she arrived at UCSF in 2012, a few years after its discovery. She reached out to Ansel, a former colleague and asthma expert who welcomed her into his lab.

First, Fassett removed the IL-31 gene from mice and exposed them to the house dust mite, a common, itchy allergen.

"We wanted to mimic what was actually happening in people who are chronically exposed to environmental allergens," Fassett said. "As we expected, the dust mite didn't cause itching in the absence of IL-31, but we were surprised to see that inflammation went up."

Why was there inflammation but no itching? Fassett and Ansel found that a cadre of immune cells had been called into action in the absence of the itch cytokine. Without IL-31, the body was blindly waging an immunological war.

A balance of forces

Ansel and Fassett then homed in on the nerve cells in the skin that received the IL-31 signal. They saw that the same nerve cells that spurred a scratch also dampened any subsequent immune response. These nerve cells were integral to keeping inflammation in check, but without IL-31, they let the immune system run wild.

Source: ScienceDaily

Allergy study on 'wild' mice challenges the hygiene hypothesis

 The notion that some level of microbial exposure might reduce our risk of developing allergies has arisen over the last few decades and has been termed the hygiene hypothesis. Now, an article published in Science Immunology by researchers from Karolinska Institutet challenges this hypothesis by showing that mice with high infectious exposures from birth have the same, if not an even greater ability to develop allergic immune responses than 'clean' laboratory mice.

How microbes may prevent allergy has been a topic of great interest in recent times. Studies have suggested that certain infections might reduce the production of inflammatory antibodies to allergens and alter the behaviour of T cells involved in allergies. It has also been suggested that good bacteria in our intestines may be able to switch off inflammation in other parts of our body.

Robust allergic responses

Researchers have now compared the allergic immune response in 'dirty' wildling mice to those of typical clean laboratory mice. They found very little evidence that the antibody response was altered or that the function of T cells changed in a meaningful way. Nor did anti-inflammatory responses evoked by good gut bacteria appear to be capable of switching off the allergic immune response. On the contrary, wildling mice developed robust signs of pathological inflammation and allergic responses when exposed to allergens.

"This was a little unexpected but suggests that it's not as simple as saying, 'dirty lifestyles will stop allergies while clean lifestyles may set them off'. There are probably very specific contexts where this is true, but it is perhaps not a general rule," says Jonathan Coquet, co-author of the study and Associate Professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet in Sweden.

More like the human immune system

The wildling mice are genetically identical to clean laboratory mice but are housed under seminatural conditions and have rich microbial exposures from birth.

"The immune systems of wildling mice better represent the human immune system and so we hope that they can bring us closer to the truth of how microbes act upon the body," says Jonathan Coquet.

The findings contribute to our general understanding of how allergies may arise and may also have clinical implications. In clinical trial settings, researchers and clinicians have recently made attempts to treat patients suffering from inflammatory diseases with experimental infections. For example, infecting people with worms or performing faecal transplantations has been proposed as a tool to combat inflammatory diseases. Newborns delivered through C-section, have had maternal faecal transplantation and bacterial supplementation with the aim of promoting good bacteria in the baby's gut and the child's future health.

Can provide important insights

"This field of research can provide important insights into how infections and microbes can be used to facilitate health, but it is still in its infancy. Our study is a reminder that general and broad exposures to microbes may not have the clear beneficial effects that we wish them to have," says Susanne Nylén, co-author of the study and Associate Professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

The work was led by Junjie Ma and Egon Urgard, researchers in Jonathan Coquet's group, and done in close collaboration with Professor Stephan Rosshart at University Medical Center Freiburg in Germany and Susanne Nylén (MTC). Several other research groups at Karolinska Institutet and elsewhere also contributed to this work, including the teams of Assistant professors Itziar Martinez Gonzalez and Juan Du (both at the Department of Microbiology, Tumor and Cell Biology, MTC).

The study was financed by several bodies, including the Swedish Research Council, the Swedish Cancer Foundation, KI intramural funds, and the Wenner-Gren Foundation.

Source: ScienceDaily

Specialized T cells may trigger severe asthma attacks in older men

 

Scientists from the University of Southampton and La Jolla Institute for Immunology (LJI), in California, have uncovered a group of immune cells that may drive severe asthma. These cells gather in the lungs and appear to cause the most harm in men who develop asthma in later life.

"If you are male and you develop asthma after age 40, there's a high chance this T cell population is in your lungs," says LJI Research Assistant Professor Gregory Seumois, who co-led the study with LJI Professor Pandurangan Vijayanand.

The new research, published in MED, suggests asthma patients with these cells in their lungs may be more likely to have hard-to-treat, and potentially fatal, asthma attacks. Normally a doctor would give an asthma patient a general therapy to dampen their immune response, but these cells don't respond to treatment.

The scientists uncovered these T cells, called 'cytotoxic CD4+ tissue-resident memory T cells', thanks to volunteers enrolled in the NHS clinic-based WATCH study. It follows hundreds of asthma patients of different ages, sexes, and disease severities. By following patients over many years, and analysing their immune cell populations, researchers are making new connections between asthma symptoms and immune cell activity.

"Once you understand the role of cells like these T cells better, you can start to develop treatments that target those cells," says WATCH study director Dr Ramesh Kurukulaaratchy, Associate Professor at the University of Southampton and researcher at the NIHR Southampton Biomedical Research Centre.

Scientists now hope to learn more about these cells and their role in asthma development in order to develop personalised therapies for asthma patients.

How harmful T cells drive asthma

The T cells are called "memory" cells because they react to molecules that the body has previously fought off. They help protect the body from viruses and bacteria, but the same T cell memory is a big problem for asthma patients. Their misguided T cells see harmless molecules, such as pollen, and produce a dangerous inflammatory response.

Men who developed asthma later in life had an overwhelming number of these potentially harmful T cells. Their lungs should have been home to a diverse bunch of CD4+ T cell types but, in this group, more than 65 per cent of their cells were cytotoxic CD4+ tissue-resident memory T cells.

Personalized asthma treatments

Single-cell RNA sequencing by LJI scientists provides a 'biomarker' to help detect cytotoxic CD4+ tissue-resident memory T cells in more patients going forward.

Finding this biomarker represents a "paradigm shift" in asthma research, says Dr Kurukulaaratchy. Before now, scientists and clinicians separated asthma patients into just two groups: 'T2 high' and T2 low'. In a study published earlier this year, the research team showed the importance of drilling down to identify many more asthma patient subgroups; their analysis reveals that 93 per cent of WATCH subjects with severe asthma were in the T2 high category.

Study co-author Professor Hasan Arshad, Chair in Allergy and Clinical Immunology at the University of Southampton, researcher at the NIHR Southampton Biomedical Research Centre, and Director of The David Hide Asthma and Allergy Research Centre, Isle of Wight says: "We have to think of severe asthma as having different subtypes, and the treatment has to be tailored according to these subtypes because one size does not fit all."

Source: ScienceDaily

Better understanding of how genes make us prone to allergies

 New research is bolstering scientific understanding behind why some people are more prone to allergies than others. Researchers in the Perelman School of Medicine at the University of Pennsylvania identified how genetic differences that alter a specific protein called ETS1 can affect our body's response to allergies. They found that small changes in ETS1 in an animal model can lead to an increased likelihood for allergic reactions that cause inflammation. The findings were published recently in Immunity.

The United States Centers for Disease Control and Prevention reports that allergies rank as the sixth most prevalent cause of chronic illness in the U.S., resulting in an annual expenditure exceeding $18 billion. While previous research has established a strong genetic basis for allergies and identified specific genetic sequence variations which predispose for these chronic diseases, how our DNA can affect our chances of developing an allergy remains unclear. But understanding this could lead to improved research and potential new treatments.

By using modern genomics and imaging techniques, a collaborative team of researchers co-led by Penn's Golnaz Vahedi, PhD, an associate professor of Genetics, and Jorge Henao-Mejia, MD, PhD, an associate professor of Pathology and Laboratory Medicine, found that the ETS1 protein plays a role in controlling a type of immune cell called CD4+ T helper cells, which are important in allergic reactions and help orchestrate the immune response by activating and coordinating other immune cells.

DNA interactions within the genomic segment encompassing the ETS1 gene control how much of the ETS1 protein is made.

"We discovered that these interactions, work like a dimmer switch," said Vahedi. "When there are changes in the DNA in this area, it can mess up the dimmer switch, causing problems with controlling the ETS1 protein. This can lead to imbalances in our immune cells and cause allergic inflammations."

While there has been progress in understanding genetic traits that follow predictable patterns, like those passed down from parents, it's been more challenging to understand conditions that involve many different genes and are common in populations. These complex conditions cannot be explained by simply "turning off" one gene. Instead, they may be caused by small changes in the DNA that affect how genes work together. However, researchers still do not know much about how these changes in DNA relate to how our genes are organized or how they affect how genes are expressed in most complex diseases.

"This work demonstrates how small differences in our DNA can disturb the balance between our immune cells, resulting in significant observable characteristics in patients. This phenomenon may occur in other common diseases such as autoimmune disorders," said Henao-Mejia.

Other co-authors of this study include Aditi Chandra, Sora Yoon, and Michael Michieletto. This research was funded by the National Institutes of Health (R01AI168240, UC4 DK112217, U01 DK112217, R01 HL145754, U01 DK127768, U01 DA052715, R01 HL136572), the Burroughs Welcome Fund, the Chan Zuckerberg Initiative Award, W. W. Smith Charitable Trust, the Sloan Foundation, and the PEW Charitable Trust.

Source: ScienceDaily

How the immune system can alter our behavior

 Simply the smell of seafood can make those with an allergy to it violently ill -- and therefore more likely to avoid it. The same avoidance behavior is exhibited by people who develop food poisoning after eating a certain meal.

Scientists have long known that the immune system played a key role in our reactions to allergens and pathogens in the environment, but it was unclear whether it played any role in prompting these types of behaviors towards allergic triggers.

According to Yale-led research published July 12 in the journal Nature, it turns out that the immune system plays a crucial role in changing our behaviors.

"We find immune recognition controls behavior, specifically defensive behaviors against toxins that are communicated first through antibodies and then to our brains," said Ruslan Medzhitov, Sterling Professor of Immunobiology at Yale School of Medicine, investigator for the Howard Hughes Medical Institute, and senior author of the study.

Without immune system communication, the brain does not warn the body about potential dangers in the environment and does not try to avoid those threats, the study shows.

A team in the Medzhitov lab, led by Esther Florsheim, at the time a postdoctoral researcher at Yale and now an assistant professor at Arizona State University, and Nathaniel Bachtel, a graduate student at the School of Medicine, studied mice that had been sensitized to have allergic reactions to ova, a protein found in chicken eggs. As expected, these mice tended to avoid water laced with ova, while control mice tended to prefer ova-laced water sources. The aversion to ova-laced water sources in sensitized mice lasted for months, they found.

The team then examined whether they could alter the behavior of sensitized mice by manipulating immune system variables. They found, for instance, that mice allergic to ova lost their aversion to the protein in their water if Immunoglobulin E (IgE) antibodies, produced by the immune system, were blocked. IgE antibodies trigger the release of mast cells, a type of white blood cell that, along with other immune system proteins, plays a crucial role in communicating to areas of the brain that control aversion behavior. Without IgE as an initiator, the transmission of information was interrupted, so that mice no longer avoided the allergen.

Medzhitov said that the findings illustrate how the immune system evolved to help animals avoid dangerous ecological niches. Understanding how the immune system memorizes potential dangers, he added, could one day help suppress excessive reactions to many allergens and other pathogens.

Source: ScienceDaily

New research shows babies' immunological weak spot and strength

 A pair of new studies led by researchers at Columbia University explains why babies get so many common respiratory infections and identifies a specialized cluster of immune cells found only in babies that help them better cope with new pathogens.

"We know little about how the immune system develops throughout life, and most of what we know about immune system development in children comes from animal studies," says Donna Farber, PhD, an expert in immune system development at Columbia University Vagelos College of Physicians and Surgeons who led the research. "But mice develop much more quickly than humans and their immune systems are a bit different than ours."

Using a trove of tissue samples from deceased pediatric organ donors, Farber's team was able to pinpoint aspects of immune system development that distinguish babies from adults.

Immune cells in lungs and gut take time to mature

One study, published in Immunity, found that specialized immune cells called memory T cells -- formed after first exposure to a pathogen -- accumulate rapidly in the lungs and intestines through age 3 and more gradually in blood and lymph tissues. These cells enable older children and adults to mount an immediate and specific immune response during the next encounter with a pathogen.

But there's a hitch.

"We found that memory T cells in young children are not functionally mature and only begin to have the capacity for protective immunity at around ages 4 to 6 years," Farber says. "This explains why babies and young children are more vulnerable to recurrent respiratory infections and other infectious diseases compared with adults."

The findings also may explain why introducing foods to children during the first year of life could prevent severe food allergies. "Early memory T cells are more tolerant than mature memory cells, so they're not going to create an immune response against new foods," Farber says.

'Secret weapon' protects babies from new pathogens

But while babies are highly susceptible to recurrent infections, a second study, published in Nature Immunology, found that babies have a unique way of coping with new pathogens. The researchers found clusters of antibody-producing B cells surrounded by T cells in the infants' lungs. This bronchus-associated lymphoid tissue, or BALT, is formed between 6 and 12 months of age and disappears after age 3.

"BALT enables the lung to make antibodies to respiratory pathogens well before T cell memory has developed but fall apart in later childhood when they are no longer needed," says Farber. "This mechanism helps young children respond to the many different respiratory pathogens they encounter early in life."

It also may explain why young kids are more resilient to new respiratory infections compared to adults -- including SARS-CoV-2.

"With SARS-CoV-2, a virus no one had ever encountered before, we saw that people in their 50s and 60s were very susceptible to severe COVID, but most kids exposed to SARS-CoV-2 were fine, and many didn't even have symptoms," Farber says. "That told us that the babies and young children must have some adaptations to respond to new pathogens that adults don't have."

BALT also may be a reason why some children develop chronic asthma and allergies. "It's possible that these diseases may be caused in part by the abnormal persistence of BALT well into childhood, which could trigger an overreaction to certain antigens," says Farber.

Farber adds that the study may provide clues about why early trials of intranasal COVID vaccines have not shown promise in adults, whereas intranasal influenza vaccine tends to work better in children. "It could be that this type of vaccine works better in children because they have BALT structures that can initiate new antibodies in the lungs."

"BALT provides some protection but clearly does not protect young children from everything," Farber continues. "We have to remember that before vaccines, a third of children died of infectious diseases during infancy. So childhood vaccines are really important for protecting us."

Source:ScienceDaily