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IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and ROR?t.

ABSTRACT: Transient thymic involution is frequently found during inflammation, yet the mode of action of inflammatory cytokines is not well defined. Here we report that interleukin-23 (IL-23) production by the thymic dendritic cells (DCs) promotes apoptosis of the CD4(hi)CD8(hi) double-positive (DP) thymocytes. A deficiency in IL-23 signalling interferes with negative selection in the male D(b)/H-Y T-cell receptor (TCR) transgenic mice. IL-23 plus TCR signalling results in significant upregulation of IL-23 receptor (IL-23R) expressed predominantly on CD4(hi)CD8(hi)CD3(+)??TCR(+) DP thymocytes, and leads to ROR?t-dependent apoptosis. These results extend the action of IL-23 beyond its peripheral effects to a unique role in TCR-mediated negative selection including elimination of natural T regulatory cells in the thymus.

SUBMITTER: Li H

PROVIDER: S-EPMC4136447 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and RORγt.

Li Hao H Hsu Hui-Chen HC Wu Qi Q Yang PingAr P Li Jun J Luo Bao B Oukka Mohamed M Steele Claude H CH Cua Daniel J DJ Grizzle William E WE Mountz John D JD

Nature communications 20140708

Transient thymic involution is frequently found during inflammation, yet the mode of action of inflammatory cytokines is not well defined. Here we report that interleukin-23 (IL-23) production by the thymic dendritic cells (DCs) promotes apoptosis of the CD4(hi)CD8(hi) double-positive (DP) thymocytes. A deficiency in IL-23 signalling interferes with negative selection in the male D(b)/H-Y T-cell receptor (TCR) transgenic mice. IL-23 plus TCR signalling results in significant upregulation of IL-2 ...[more]

PMID: 25001511

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