Autoimmune diseases are widespread and notoriously difficult to treat. In part, this is because why the immune system attacks its own tissues in patients with these conditions remains poorly understood.
In a study recently published in Cell, researchers from Osaka University have revealed that the body’s own proteins with unusual structure trigger immune cells to unleash a wave of inflammation that leads to autoimmunity.
Autoimmune diseases develop when the body’s immune system mistakenly attacks its own tissues instead of fighting off foreign invaders like bacteria or viruses. However, it has long been a mystery why this happens, as the immune system has many checks and balances to make sure that it only reacts to ‘non-self’ triggers.
“T cells have been thought to discriminate between small fragments of protein derived from self and non-self proteins presented on the major histocompatibility complex II (MHC-II), and ‘trained’ not to respond self-antigens” explains senior author of the study Hisashi Arase.
However, when the MHC-II is missing a crucial piece called the invariant chain (Ii), it can present larger, misfolded self antigens, called neoself-antigens, to T cells.”
Hisashi Arase, Osaka University
Given that autoantibodies to neoself-antigens are frequently found in patients with autoimmune diseases, the researchers explored T cell reactivity in patients with lupus and in mice, in which Ii was depleted from adult. They also investigated the effect of Epstein–Barr virus (EBV) infection, a risk factor for lupus, on T cell reactivity to neoself-antigens.
“The results were striking,” says Shunsuke Mori, lead author. “We found that approximately 10% of clonally expanded T cell repertoire in lupus patients recognized neoself-antigens. Furthermore, induction of neoself-antigens induced lupus-like disease in mice, meaning that they mounted an immune response to the body’s own tissues, thereby causing autoimmune disease.”
Furthermore, the researchers found that reactivation of EBV, which most people are infected with but is usually dormant, increases the presentation of neoself-antigens on MHC-II through downregulating the expression of Ii, triggering the activation of T cells directed against the body. This could explain why EBV reactivation is linked to the onset or exacerbation of lupus.
“Our findings demonstrate that T cells discriminate self- and neoself-antigens and do not recognize neoself-antigens as self antigens, thus leading to the development of autoimmunity when neoself-antigens are presented on MHC-II,” says Arase.
This study substantially increases our understanding of self-tolerance of T cells as well as the causes of autoimmune disease by identifying neoself-antigens as a distinct class of antigens that trigger an inappropriate immune response. This insight into why the body begins to attack itself could help develop new treatments for autoimmune disorders like lupus.
Mori, S., et al. (2024) Neoself-antigens are the primary target for autoreactive T cells in human lupus. Cell. doi.org/10.1016/j.cell.2024.08.025.
News
Two Hidden Forces Help Build the Human Brain Before Birth
Scientists have uncovered two surprising forces that help guide how the human brain forms before birth. Before birth, the human brain is shaped in large part by an unusual class of stem cells known [...]
Researchers Uncover a Hidden Trigger Behind Chronic Inflammation
The findings offer new insights that could help guide the development of future therapies. A protein called human resistin may help flip on one of the immune system’s most powerful inflammatory switches. Researchers at [...]
Scientists Have Uncovered Previously Hidden Microbial Activity on Human Skin
The most abundant microbes on your skin may not be the ones doing most of the work. Human skin supports vast communities of bacteria, fungi, and viruses that can influence its protective barrier, immune [...]
Brazilian Tree Compounds Fight COVID-19 on Multiple Fronts
Scientists found compounds in a Brazilian tree that hit SARS-CoV-2 on multiple fronts, revealing a promising new lead in the search for COVID-19 treatments. Researchers have found that galloylquinic acids extracted from the leaves [...]
Cutting Two Amino Acids Slowed Prostate Cancer in Mice
A newly identified link between amino acid metabolism and cholesterol production may help prostate tumors adapt to hormone therapy. Prostate cancer can find ways around treatments designed to deprive tumors of the hormones they [...]
Largest-Ever Physics Survey Raises New Doubts About Our Model of the Universe
Physicists around the world remain deeply divided on key mysteries of the universe, from dark matter to quantum gravity. The standard cosmological model failed to gain majority support, and no leading theory dominated the [...]
Scientists Just Overturned a 100-Year-Old Belief About Bacteria in the Lungs
New findings raise questions about the role of microbes living in the lungs. More than 35 trillion bacteria live throughout the human body, forming microbiomes in the gut, mouth, lungs, skin, and urogenital tract. [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Novartis, Ionis drug failure spurs questions
Pelacarsen didn’t protect heart health despite lowering levels of a protein particle, “Lp(a),” in a large clinical trial — a result with important implications for cardiovascular drug research. Dive Brief: An RNA drug from [...]
New injectable treatment helps the brain rebuild after stroke
Biomedical engineers at Duke University have created an injectable biomaterial that may help the brain recover from damage left behind by an ischemic stroke. In experiments with mice, the material transformed the cavity created [...]
Scientists Discover a Hidden “Immune Organ” Inside the Skull
Researchers discovered lymph node-like immune hubs inside skull bone marrow that appear to act as rapid-response centers for the brain. For decades, the brain was thought to operate largely apart from the immune system. [...]
Engineered tRNAs and lipid nanoparticles target nonsense mutation cystic fibrosis
Researchers have developed a potential new approach for treating a form of cystic fibrosis caused by so-called nonsense mutations, combining chemically modified transfer RNAs with lipid nanoparticles designed to deliver the therapy directly to [...]
New pancreatic cancer drug carries a $39,800 monthly list price
A groundbreaking treatment for one of the most common forms of pancreatic cancer has been approved in pill form by the FDA. Revolution Medicines’ oral tablet daraxonrasib, branded as Rasonque, reduced the risk of [...]
Researchers Have Discovered a New Way To Reduce Chronic Nerve Pain
A cancer-linked protein called BRAF may help drive chronic nerve pain, and existing cancer drugs targeting it reduced pain sensitivity in preclinical models. Chronic nerve pain can persist long after an injury and often [...]
Our books now available worldwide!
Online Sellers other than Amazon, Routledge, and IOPP Indigo Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artifcial Intelligence Global Health Care Equivalency In The Age Of Nanotechnology, Nanomedicine And Artificial [...]
Quantum-Enabled Regenerative Health: Reimagining Wellness, Precision Health and Longevity Medicine
Introduction Healthcare is approaching a frontier where the quantum portfolio could influence not only how disease is diagnosed and treated, but how health itself is measured, modeled, predicted and preserved. Quantum computing, quantum simulation, [...]
