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Central immune tolerance depends on crosstalk between the classical and alternative NF-κB pathways in medullary thymic epithelial cells

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Item Type:Article
Title:Central immune tolerance depends on crosstalk between the classical and alternative NF-κB pathways in medullary thymic epithelial cells
Creators Name:Riemann, M. and Andreas, N. and Fedoseeva, M. and Meier, E. and Weih, D. and Freytag, H. and Schmidt-Ullrich, R. and Klein, U. and Wang, Z.Q. and Weih, F.
Abstract:Medullary thymic epithelial cells (mTECs) contribute to self-tolerance by expressing and presenting peripheral tissue antigens for negative selection of autoreactive T cells and differentiation of natural regulatory T cells. The molecular control of mTEC development remains incompletely understood. We here demonstrate by TEC-specific gene manipulation in mice that the NF-{kappa}B transcription factor subunit RelB, which is activated by the alternative NF-{kappa}B pathway, regulates development of mature mTECs in a dose-dependent manner. Mice with conditional deletion of Relb lacked mature mTECs and developed spontaneous autoimmunity. In addition, the NF-{kappa}B subunits RelA and c-Rel, which are both activated by classical NF-{kappa}B signaling, were jointly required for mTEC differentiation by directly regulating the transcription of Relb. Our data reveal a crosstalk mechanism between classical and alternative NF-{kappa}B pathways that tightly controls the development of mature mTECs to ensure self-tolerance.
Keywords:Autoimmunity, Central Immune Tolerance, Medullary Thymic Epithelial Cells, NF-{kappa}B, Conditional Gene Targeting, Animals, Mice
Source:Journal of Autoimmunity
ISSN:0896-8411
Publisher:Elsevier / Academic Press (U.K.)
Volume:81
Page Range:56-67
Date:July 2017
Official Publication:https://doi.org/10.1016/j.jaut.2017.03.007
PubMed:View item in PubMed

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