title: Regulations of gene expression in medullary thymic epithelial cells required for preventing the onset of autoimmune diseases.
abstract: Elimination of potential self-reactive T cells in the thymus is crucial for preventing the onset of autoimmune diseases. Epithelial cell subsets localized in thymic medulla [medullary thymic epithelial cells (mTECs)] contribute to this process by supplying a wide range of self-antigens that are otherwise expressed in a tissue-specific manner (TSAs). Expression of some TSAs in mTECs is controlled by the autoimmune regulator (AIRE) protein, of which dysfunctional mutations are the causative factor of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). In addition to the elimination of self-reactive T cells, recent studies indicated roles of mTECs in the development of Foxp3-positive regulatory T cells, which suppress autoimmunity and excess immune reactions in peripheral tissues. The TNF family cytokines, RANK ligand, CD40 ligand, and lymphotoxin were found to promote the differentiation of AIRE- and TSA-expressing mTECs. Furthermore, activation of NF-κB is essential for mTEC differentiation. In this mini-review, we focus on molecular mechanisms that regulate induction of AIRE and TSA expression and discuss possible contributions of these mechanisms to prevent the onset of autoimmune diseases.
authors.affiliation: Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo , Tokyo , Japan.
authors.forename: Taishin
authors.initials: T
authors.lastname: Akiyama
authors.forename: Miho
authors.initials: M
authors.lastname: Shinzawa
authors.forename: Junwen
authors.initials: J
authors.lastname: Qin
authors.forename: Nobuko
authors.initials: N
authors.lastname: Akiyama
keywords: NF-κB; TNF receptor family; autoimmune disease; gene expression; medullary thymic epithelial cells