Thymic self-antigen expression for immune tolerance and surveillance
Open Access
- 3 September 2022
- journal article
- review article
- Published by Springer Nature in Inflammation and Regeneration
- Vol. 42 (1) , 1-10
Abstract
T cells are a group of lymphocytes that play a central role in the immune system, notably, eliminating pathogens and attacking cancer while being tolerant of the self. Elucidating how immune tolerance is ensured has become a significant research issue for understanding the pathogenesis of autoimmune diseases as well as cancer immunity. T cell immune tolerance is established mainly in the thymic medulla by the removal of self-responsive T cells and the generation of regulatory T cells, this process depends mainly on the expression of a variety of tissue restricted antigens (TRAs) by medullary thymic epithelial cells (mTECs). The expression of TRAs is known to be regulated by at least two independent factors, Fezf2 and Aire, which play non-redundant and complementary roles by different mechanisms. In this review, we introduce the molecular logic of thymic self-antigen expression that underlies T cell selection for the prevention of autoimmunity and the establishment of immune surveillance.Keywords
Funding Information
- Japan Society for the Promotion of Science (17K19545, 20K21514, 20H03465)
- Shimadzu Science Foundation
This publication has 105 references indexed in Scilit:
- Plasmacytoid Dendritic Cells Transport Peripheral Antigens to the Thymus to Promote Central ToleranceImmunity, 2012
- Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cellsProceedings of the National Academy of Sciences, 2011
- T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouseJournal of Experimental Medicine, 2011
- Regulatory T cell differentiation of thymocytes does not require a dedicated antigen-presenting cell but is under T cell-intrinsic developmental controlProceedings of the National Academy of Sciences, 2009
- Thymus-homing peripheral dendritic cells constitute two of the three major subsets of dendritic cells in the steady-state thymusJournal of Experimental Medicine, 2009
- Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunityProceedings of the National Academy of Sciences, 2008
- The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expressionEMBO Reports, 2008
- Linked T Cell Receptor and Cytokine Signaling Govern the Development of the Regulatory T Cell RepertoireImmunity, 2008
- A Two-Step Process for Thymic Regulatory T Cell DevelopmentImmunity, 2008
- DNA-PK contributes to the phosphorylation of AIRE: Importance in transcriptional activityBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2008