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

Academic Article

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(+)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.
  • Published In

    Keywords

  • Animals, Apoptosis, Interleukin-23, Male, Mice, Inbred C57BL, Mice, Transgenic, Nuclear Receptor Subfamily 1, Group F, Member 3, Receptors, Antigen, T-Cell, Receptors, Interleukin, Thymocytes
  • Digital Object Identifier (doi)

    Author List

  • Li H; Hsu H-C; Wu Q; Yang P; Li J; Luo B; Oukka M; Steele CH; Cua DJ; Grizzle WE
  • Start Page

  • 4259
  • Volume

  • 5