January 11, 2022
Keio University School of Medicine
A research team from the Department of Dermatology, Keio University School of Medicine, led by Collaborative Researcher Keigo Iriki (a graduate student at the time of the research), Associate Professor Hayato Takahashi, and Professor Masayuki Amagai, has discovered a new mechanism in the lymph nodes that eliminates T cells attacking the body's own epidermal proteins.
Humans are equipped with an immune system to eliminate pathogens. This system is diverse enough to fight off various viruses and bacteria, but it also has a mechanism to prevent it from mistakenly attacking the body's own cells. This is known as the immunological tolerance mechanism. When this mechanism fails and self-reactive T cells are produced, they attack the body, leading to tissue damage and the development of autoimmune diseases. The immunological tolerance mechanism is broadly divided into a "central mechanism," which operates primarily in the thymus where immune cells are developed, and a "peripheral mechanism," which functions in peripheral tissues when immune cells are about to attack their target antigens.
In this study, the research team analyzed the peripheral mechanism of immunological tolerance to desmoglein 3 (Dsg3), an adhesion protein in skin cells that is the target of the immune system in the autoimmune disease pemphigus vulgaris. The results revealed the existence of a mechanism in the periphery that eliminates Dsg3-reactive T cells that have escaped removal by the central mechanism. They also found that a molecule called OX40, present on regulatory T cells, plays an essential role in this mechanism. The findings of this basic research shed light on one of the sophisticated mechanisms that keep the human body healthy and could lead to the development of new treatments and prevention methods for autoimmune diseases.
The results of this research were published in the American scientific journal "Proceedings of the National Academy of Sciences" on December 7, 2021 (U.S. Central Standard Time).
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