MINI REVIEW ARTICLE
Front. Immunol., 26 August 2013 | doi: 10.3389/fimmu.2013.00249
Regulations of gene expression in medullary thymic epithelial cells required for preventing the onset of autoimmune diseases
- 1Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
- 2Key Laboratory for Regenerative Medicine, Department of Developmental and Regenerative Biology, Ministry of Education and International Base of Collaboration for Science and Technology, the Ministry of Science and Technology and Guangdong Province, Jinan University, Guangzhou, China
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.
Keywords: medullary thymic epithelial cells, autoimmune disease, NF-κB, TNF receptor family, gene expression
Citation: Akiyama T, Shinzawa M, Qin J and Akiyama N (2013) Regulations of gene expression in medullary thymic epithelial cells required for preventing the onset of autoimmune diseases. Front. Immunol. 4:249. doi: 10.3389/fimmu.2013.00249
Received: 07 June 2013; Paper pending published: 24 June 2013;
Accepted: 09 August 2013; Published online: 26 August 2013.
Accepted: 09 August 2013; Published online: 26 August 2013.
Edited by:
Claudio Pignata, Federico II University, Italy
Reviewed by:
Anna Villa, National Council of Research, ItalyPetteri Arstila, University of Helsinki, Finland
Copyright: © 2013 Akiyama, Shinzawa, Qin and Akiyama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Taishin Akiyama, Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan e-mail: taishin@ims.u-tokyo.ac.jp
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