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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-07-08

AUTHORS

Hao Li, Hui-Chen Hsu, Qi Wu, PingAr Yang, Jun Li, Bao Luo, Mohamed Oukka, Claude H. Steele, Daniel J. Cua, William E. Grizzle, John D. Mountz

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 CD4hiCD8hi double-positive (DP) thymocytes. A deficiency in IL-23 signalling interferes with negative selection in the male Db/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 CD4hiCD8hiCD3+αβTCR+ DP thymocytes, and leads to RORγt-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. More... »

PAGES

4259

References to SciGraph publications

  • <error retrieving object. in <ERROR RETRIEVING OBJECT
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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1038/ncomms5259

    DOI

    http://dx.doi.org/10.1038/ncomms5259

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25001511


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    30 schema:description 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 CD4hiCD8hi double-positive (DP) thymocytes. A deficiency in IL-23 signalling interferes with negative selection in the male Db/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 CD4hiCD8hiCD3+αβTCR+ DP thymocytes, and leads to RORγt-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.
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