Riemann, M, Andreas, N, Fedoseeva, M et al. (7 more authors) (2017) Central immune tolerance depends on crosstalk between the classical and alternative NF-κB pathways in medullary thymic epithelial cells. Journal of Autoimmunity, 81. pp. 56-67. ISSN 0896-8411
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-κB transcription factor subunit RelB, which is activated by the alternative NF-κB 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-κB subunits RelA and c-Rel, which are both activated by classical NF-κB 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-κB pathways that tightly controls the development of mature mTECs to ensure self-tolerance.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | Autoimmunity; Central immune tolerance; Medullary thymic epithelial cells; NF-κBConditional gene targeting |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Haematology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 16 Aug 2018 12:14 |
Last Modified: | 16 Aug 2018 12:14 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jaut.2017.03.007 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:134665 |