Laboratory for Immune Homeostasis

Research Interests

Research on the mechanisms that inhibit the onset of autoimmune diseases

 

T lymphocytes (T cells) are important for immune responses against bacteria and viruses (foreign antigens). Most of them are produced in a tissue called the thymus. The thymus is the primary lymphoid organ that covers the heart.

 

T cell production in the thymus produces T cells that react not only to foreign antigens but also to proteins in the body's own tissues (autoreactive T cells). When autoreactive T cells trigger an immune response, autoimmune diseases develop.

Fortunately, most of the autoreactive T cells are eliminated in the thymus and the development of autoimmune diseases is prevented.

The principle is simple. When T cells produced in the thymus recognize self-antigens within the thymus, they are considered autoreactive T cells and are eliminated.

 

Trouble is, there are some problems with this mechanism. That is, for this mechanism to work, the self-antigen must be expressed in the thymus. For example, for proteins such as insulin, which are expressed and function only in the pancreas, this mechanism cannot work, resulting in autoimmune diseases such as type I diabetes.

 

The cells that solve this problem are "thymic medullary epithelial cells" (hereafter referred to as medullary epithelial cells, mTECs). Medullary epithelial cells are epithelial cells localized in the interior of the thymus (medulla) and are found only in a small number in the thymus.

 

Medullary epithelial cells, however, have a very unique characteristic that other cells do not have. They ectopically express a very large variety of proteins (tissue-specific autoantigens) that are expressed only in other tissues of the body (pancreas, liver, etc.).

This property also allows, for example, autoreactive T cells that respond to insulin to recognize and eliminate insulin in the thymus, thus preventing the onset of diabetes.

Importantly, it has also been shown that when these medullary epithelial cells become abnormal, autoimmune diseases develop.

 

It is clear that medullary epithelial cells are important in suppressing the development of autoimmune diseases. However, the mechanism by which they "ectopically" express tissue-specific autoantigens is not well understood. We are currently trying to elucidate the mechanism.

 

 

We welcome anyone who is interested in working together with us.