A recent study found the lymph node cells, much like the thymus, play a part in immune self-tolerance.
Nearly 5% of the U.S. population is affected with a devastating autoimmune disease, and this percentage is ever growing. Current treatments address organ inflammation or approach the autoimmunity with immunosuppression, which has serious and widespread side effects. In order to develop more specific and effective therapies, there must be a fuller understanding of the mechanisms by which self-tolerance develops. It is known that autoimmune diseases occur due to the immune system’s loss of tolerance to self-antigens. How and why this loss of tolerance occurs is associated with many factors, including genetic (and epigenetic), cellular, environmental, and more.
Research over the years has uncovered the role of the thymus in generating self-antigens and in the elimination of T cells reacting to these. A defect in this process leads to autoimmune disease. One explanation may be a mutation of the Aire gene, which regulates the expression of self-antigens in medullary thymic epithelial cells. The resulting decrease in expression leads to less production of self-antigens, impaired presentation of the antigens to auto-reactive T cells, and diminished elimination of the T cells.
However, a group of scientists at Kanazawa University found that the thymus is not the only tissue where the Aire gene is expressed. Using laboratory mice and antibodies to Aire gene products, the researchers found that a small percentage of cells in peripheral lymph nodes express the Aire gene. They studied the morphological and molecular characteristics of these cells and determined that they resemble group 3 innate lymphoid cells involved in innate defense on mucous membranes.
When Aire-expressing cells of mice expressed the influenza virus antigen, the cells eliminated the T cells that reacted to the virus antigen. Therefore, these cells of peripheral lymph nodes are involved in immune self-tolerance. This new mechanistic information can help bring us closer to understanding how autoimmunity is developed, leading to more effective and safer therapies for autoimmune diseases.
Reference: Identification of lymph node cells that may play important roles in immune tolerance. (1554). EurekAlert!. Retrieved 21 May 2019, from https://www.eurekalert.org/pub_releases/2019-04/ku-iol040919.php