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Allergy

The Missing Link in Autoimmune Disorders: Researchers Identify Key Protein in Immune Response

Scientists have identified a protein in cells that spurs the release of infection-fighting molecules. The protein, whose role in the immune system had not previously been suspected, provides a potential target for therapies that could prevent over-reactive immune responses that are at the root of several debilitating illnesses.

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The autoimmune disease affects millions of people worldwide, where the body mistakenly attacks healthy tissues due to an overactive immune response. Scientists have long understood how false alarms are triggered, but the subsequent step of dispatching the immune response has remained a mystery. Researchers at Washington University School of Medicine and the Perelman School of Medicine at the University of Pennsylvania have now identified a crucial component in launching the immune activity – and its overactivity.

The researchers discovered that ArfGAP2, a protein found in cells, is responsible for spurring the release of infection-fighting molecules. This protein’s role in the immune system was previously unknown, making it a promising target for therapies to prevent overreactive immune responses at the root of several debilitating illnesses. Their study, published online in Cell, highlights the potential for treating autoimmune disorders by controlling the release process.

By studying a rare autoimmune disease called STING-associated vasculopathy with onset in infancy (SAVI), researchers gained insight into how this condition occurs due to changes in the protein STING. This protein acts as a molecular watchdog that responds to viral DNA, activating the cell’s immune proteins and signaling to the body’s immune system where to attack.

The team made a groundbreaking discovery: ArfGAP2 plays a novel role in releasing immune response proteins from cells, which was previously unknown. In addition, they validated this finding by testing it in SAVI cells that did not produce ArfGAP2. Without this protein, STING could not drive the release of immune proteins.

“This is like a train station and ArfGAP2 is acting as the conductor, directing which molecules are to be shipped out,” said David Kast, an assistant professor at WashU Medicine. “If STING and ArfGAP2 are not working together, the trains are stopped.”

The researchers tested this idea by genetically modifying mice with SAVI, but without producing the ArfGAP2 protein. They found that the lung- and limb-destroying immune response typical of the disease did not occur, confirming that neutralizing this protein could turn off the overactive immune response.

This breakthrough has significant implications for treating other conditions that lead to excess immune proteins, such as cytokine storms in COVID-19 or brain inflammation linked to immune responses in Alzheimer’s disease. As Jonathan Miner, an associate professor at Penn’s Colter Center for Autoimmunity, said, “Diseases like SAVI that are super rare can provide valuable insights… Suddenly you’ve opened the doors to all these new avenues of potential therapies for many, many different classes of diseases.”

Allergy

The Hidden Dangers of Fire Smoke Exposure

Smoke from wildfires and structural fires doesn t just irritate lungs it actually changes your immune system. Harvard scientists found that even healthy people exposed to smoke showed signs of immune system activation, genetic changes tied to allergies, and even toxic metals inside their immune cells.

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The dangers of fire smoke exposure are well-documented, but until now, the full extent of its impact on our bodies has been unclear. A recent study led by researchers at Harvard T.H. Chan School of Public Health reveals that fire smoke can alter our immune system on a cellular level, leaving lasting changes and increasing our risk of serious health problems.

The study examined blood samples from 31 individuals who had been exposed to fire smoke and compared them to those from 29 non-exposed individuals. The results showed significant changes in the immune cells of those who had been exposed to smoke. These changes included an increase in memory CD8+ T cells, which are crucial for long-term immunity against pathogens, as well as elevated activation and chemokine receptor biomarkers that indicate inflammation and immune activity.

The researchers also found changes in 133 genes related to allergies and asthma in the individuals who had been exposed to smoke. Moreover, their immune cells were more likely to be bound with toxic metals like mercury and cadmium, which can further harm our health.

“This study fills a critical knowledge gap by showing exactly how fire smoke exposure can damage the body,” said Kari Nadeau, corresponding author of the study and chair of the Department of Environmental Health. “Our findings have significant implications for public health leaders and clinicians who need to respond to the growing threat of wildfires.”
The study’s lead author, Mary Johnson, added that the immune system is extremely sensitive to environmental exposures like fire smoke, even in healthy individuals. Knowing exactly how smoke exposure can harm our bodies may help us detect immune dysfunction earlier and pave the way for new therapeutics to mitigate or prevent the health effects of smoke exposure.

The researchers also noted that their study could inform environmental and public health policies and investments, such as increasing public awareness about the dangers of smoke exposure and the importance of following evacuation procedures during wildfires.
The study was funded by several organizations, including the National Institute of Environmental Health Sciences, the National Heart, Lung, and Blood Institute, and the San Francisco Cancer Prevention Foundation.

In conclusion, this study highlights the need for increased caution when it comes to fire smoke exposure. By understanding the full extent of its impact on our bodies, we can take steps to protect ourselves and others from its toxic effects.

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Allergy

The Resilient Enemy: Why Asthma Symptoms Persist Despite Powerful Drugs

Biological drugs have been a game-changer for people with severe asthma, helping them breathe easier and live more comfortably. But researchers at Karolinska Institutet have uncovered a surprising twist: while these treatments ease symptoms, they may not fully eliminate the immune cells that drive inflammation. In fact, some of these cells actually increase during treatment, suggesting the medication is managing symptoms without targeting the root cause. This could explain why asthma often returns when the drugs are stopped, raising questions about how long-term these treatments should be and whether we’re truly solving the underlying problem.

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Asthma has long been a formidable foe for many people, causing symptoms that can range from mild discomfort to life-threatening attacks. While powerful biological drugs have significantly improved the lives of those with severe asthma, a recent study has shed light on why these symptoms often return despite treatment.

Biological drugs, or biologics, have become a crucial tool in managing severe asthma by helping patients keep their symptoms under control. However, researchers at Karolinska Institutet in Sweden discovered that certain immune cells, which play a significant role in asthma inflammation, do not disappear during treatment as previously thought. Instead, these inflammatory cells increase in number.

This finding suggests that biologics might not address the root cause of asthma, but rather manage its symptoms. As such, continued treatment may be necessary to keep the disease under control. This is particularly concerning considering that little is still known about the long-term effects of biologics like mepolizumab and dupilumab, which have been prescribed to asthmatics for less than ten years.

The study analyzed blood samples from 40 patients before and during treatment, using advanced methods such as flow cytometry and single-cell sequencing. Researchers were surprised to find that the levels of inflammatory cells in these patients increased rather than decreased. This could explain why inflammation of the airways often returns when the treatment is tapered or discontinued.

It is essential for researchers and medical professionals to understand the long-term immunological effects of biologics, as this knowledge can lead to more effective treatments and better outcomes for patients with severe asthma. The next stage of the study will involve analyzing samples from patients with a long treatment history and studying lung tissue to see how immune cells are affected in the airways.

The findings of this study have significant implications for the management and treatment of asthma, highlighting the need for continued research into the effects of biologics on the immune system.

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Allergy

Uncovering the Secrets of Urban Allergies: How Environmental Factors Shape Immunity and Increase the Risk of Allergic Diseases

Evidence of a unique T cell may explain why urban children are more prone to allergies than rural children. Differences in the development of the gut microbiome may be an underlying cause.

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The scientific community has long been aware that children growing up in urban areas are more prone to allergies than their rural counterparts. However, the exact reasons behind this disparity have remained unclear until recently. A groundbreaking study published in the journal Allergy sheds new light on how environmental factors shape the immune system and contribute to the increased risk of allergic diseases in urban children.

Researchers from the University of Rochester Medical Center (URMC) Department of Pediatrics discovered a previously uncharacterized subset of immune cells known as helper 2 (Th2) cells that play a critical role in the development of allergic diseases. These aggressive Th2 cells are more inflammatory than any other type of T-cell, and their presence is associated with an increased likelihood of developing allergies.

The study compared blood samples from urban infants with those from infants living in a farming community, known for its low rates of allergies. The findings revealed that while urban infants had higher levels of aggressive Th2 cells, the farming infants had more regulatory T-cells that help keep the immune system in balance and reduce the likelihood of allergic responses.

The lead researcher, Dr. Kirsi Järvinen-Seppo, speculates that differences in the development of the gut microbiome between the two populations may be a key factor contributing to this disparity. She suggests that exposure to “healthy” bacteria in rural environments may promote the development of a more tolerant immune system, while urban environments may prime immune cells for allergic inflammation.

This study is part of a broader investigation into how early-life exposures influence long-term immune outcomes. The researchers received a $7 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) to continue their work in identifying protective factors that could be translated into preventive therapies, including probiotics or microbiome-supporting interventions.

The discovery of these aggressive Th2 cells and their association with urban allergies provides new insight into how environmental factors shape the immune system. As researchers continue to explore this area, they may uncover solutions to prevent allergic disease development in at-risk children.

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