Autoimmune-mediated thymic atrophy is accelerated but reversible in RelB-deficient mice

O’Sullivan, Brendan J., Yekollu, Suman, Ruscher, Roland, Mehdi, Ahmed M., Maradana, Muralidhara Rao, Chidgey, Ann P., and Thomas, Ranjeny (2018) Autoimmune-mediated thymic atrophy is accelerated but reversible in RelB-deficient mice. Frontiers in Immunology, 9. 1092.

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Polymorphisms impacting thymic function may decrease peripheral tolerance and hasten autoimmune disease. The NF-κB transcription factor subunit, RelB, is essential for the development and differentiation of medullary thymic epithelial cells (mTECs): RelB-deficient mice have reduced thymic cellularity and markedly fewer mTECs, lacking AIRE. The precise mechanism of this mTEC reduction in the absence of RelB is unclear. To address this, we studied mTECs and dendritic cells (DCs), which critically regulate negative selection, and thymic regulatory T-cells (tTreg) in RelB−/− mice, which have spontaneous multiorgan autoimmune disease. RelB−/− thymi were organized, with medullary structures containing AIRE− mTECs, DCs, and CD4+ thymocytes, but fewer tTreg. Granulocytes infiltrated the RelB−/− thymic cortex, capsule, and medulla, producing inflammatory thymic medullary atrophy, which could be treated by granulocyte depletion or RelB+ DC immunotherapy, with concomitant recovery of mTEC and tTreg numbers. These data indicate that central tolerance defects may be accelerated by autoimmune thymic inflammation where impaired RelB signaling impairs the medullary niche, and may be reversible by therapies enhancing peripheral Treg or suppressing inflammation.

Item ID: 60652
Item Type: Article (Research - C1)
ISSN: 1664-3224
Copyright Information: Copyright © 2018 O’Sullivan, Yekollu, Ruscher, Mehdi, Maradana, Chidgey and Thomas. 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) and the copyright owner 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.
Date Deposited: 22 Oct 2019 02:42
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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