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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 Silent Invader: How a Parasitic Worm Evades Detection and What it Can Teach Us About Pain Relief”

Scientists have discovered a parasite that can sneak into your skin without you feeling a thing. The worm, Schistosoma mansoni, has evolved a way to switch off the body’s pain and itch signals, letting it invade undetected. By blocking certain nerve pathways, it avoids triggering the immune system’s alarms. This stealth tactic not only helps the worm survive, but could inspire new kinds of pain treatments and even preventative creams to protect people from infection.

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A new study published in The Journal of Immunology has made an intriguing discovery about how a parasitic worm evades detection and what it can teach us about pain relief. Researchers from Tulane School of Medicine found that the Schistosoma mansoni worm, which causes schistosomiasis, suppresses neurons in the skin to avoid triggering an immune response.

When this worm penetrates human skin, typically through contact with infested water, it produces molecules that block a protein called TRPV1+, which is responsible for sending pain signals to the brain. This clever mechanism allows the worm to infect the skin largely undetected.

The researchers believe that the S. mansoni worm evolved this strategy to enhance its own survival and found that blocking TRPV1+ also reduced disease severity in mice infected with the parasite. The study suggests that identifying the molecules responsible for suppressing TRPV1+ could lead to new painkillers that do not rely on opioids.

Moreover, the researchers discovered that TRPV1+ is essential for initiating host protection against S. mansoni infection. When this protein is activated, it triggers a rapid mobilization of immune cells, which induces inflammation and helps fight off the parasite. This finding highlights the critical role of neurons in pain-sensing and immune responses.

The study’s lead author, Dr. De’Broski R. Herbert, emphasizes that identifying these molecules could inform preventive treatments for schistosomiasis. He envisions a topical agent that activates TRPV1+ to prevent infection from contaminated water for individuals at risk of acquiring S. mansoni.

This groundbreaking research has the potential to revolutionize our understanding of pain relief and immune responses, offering new avenues for developing innovative therapies that could benefit millions worldwide.

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Allergy

Flossing for Vaccines: A New Method to Deliver Immunizations

Scientists have discovered that flossing between your teeth could one day help vaccinate you. By targeting a uniquely permeable gum tissue called the junctional epithelium, this new method stimulates immunity right where many infections enter: the mouth, nose, and lungs. Using dental floss on mice to apply a flu vaccine triggered a robust immune response—better than existing oral approaches and comparable to nasal vaccines, but without the risks. It even worked with mRNA and protein-based vaccines.

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The article “Flossing for Vaccines: A New Method to Deliver Immunizations” discusses a novel technique developed by researchers to deliver vaccines via dental floss. The method targets the junctional epithelium, a thin layer of tissue between the tooth and gum, which lacks barrier features and is more permeable than other epithelial tissues. This allows for enhanced antibody production across the body’s mucosal layers.

The researchers applied vaccine-coated floss to lab mice and compared antibody production in three different methods: via the junctional epithelium, nasal epithelium, or under the tongue. They found that applying vaccine via the junctional epithelium produced a superior antibody response on mucosal surfaces than the current gold standard for vaccinating via the oral cavity.

This technique has significant advantages beyond improved antibody response on mucosal surfaces. It is easy to administer and addresses concerns many people have about being vaccinated with needles. The researchers also believe this method should be comparable in price to other vaccine delivery techniques.

However, there are some drawbacks to consider. This technique would not work on infants and toddlers who do not yet have teeth. Additionally, the approach may not be suitable for people with gum disease or other oral infections, and more research is needed to fully understand its potential benefits and limitations.

The study was published in the journal Nature Biomedical Engineering and was supported by grants from the National Institutes of Health and funds from the Whitacre Endowed Chair in Science and Engineering at Texas Tech University. The researchers are optimistic about this work and may move toward clinical trials depending on their findings.

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Allergy

Nature’s Longevity Hack: How Human Eggs Stay Fresh for 50 Years

Human eggs stay dormant for decades by slowing down their waste disposal systems, according to new research involving over 100 freshly donated eggs. This clever energy-saving strategy appears to help protect the eggs from damage over time, allowing them to remain viable for years.

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In a groundbreaking study published in The EMBO Journal, researchers have uncovered the remarkable secret behind human eggs’ ability to remain viable for up to 50 years. By examining over 100 freshly donated eggs from 21 healthy donors aged 19-34, scientists have discovered that these cells deliberately slow down their internal waste disposal systems as they mature.

This “longevity hack” allows the eggs to maintain a low metabolic rate and minimize damage caused by reactive oxygen species (ROS), harmful molecules that can damage DNA and membranes. The study’s corresponding author, Dr. Elvan Böke, explains that this strategy is likely an evolutionary design that keeps the cells pristine for many years.

The research highlights the importance of protein recycling in maintaining cellular health. Lysosomes and proteasomes are the cell’s main waste disposal units, but every time they degrade proteins, they consume energy, which can lead to ROS production. By tapping the brakes on recycling, the egg keeps ROS production to a minimum while still doing enough housekeeping to survive.

This study builds upon previous research by Dr. Böke’s group, published in 2022, which showed that human oocytes deliberately skip a fundamental metabolic reaction to curb ROS production. Together, these studies suggest that human eggs power down in different ways to keep potential damage as low as possible for as long as possible.

The researchers’ findings have significant implications for fertility treatments and IVF success rates. By understanding how human eggs maintain their quality over time, scientists can develop new strategies to improve the chances of pregnancy. Dr. Böke notes that current advice for fertility patients often involves taking random supplements to improve egg metabolism, but evidence for any benefit is patchy.

In contrast, this study suggests that maintaining the egg’s naturally quiet metabolism could be a better approach for preserving quality. The researchers now plan to examine eggs from older donors and failed IVF cycles to see whether throttling the activity of cellular waste disposal units falters with age or disease.

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