Regulation of IL-17 expression by the developmental pathway of CD4 T cells in the thymus

M. Hanief Sofi, Zhiping Liu, Lingqiao Zhu, Qiao Yu, Mark H. Kaplan, Cheong Hee Chang

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

CD4 T cells selected by MHC class II expressing thymocytes (T-CD4 T cells) have distinct effector functions compared to that of epithelial cell-selected CD4 T cells (E-CD4 T cells). T-CD4 T cells produce both Th1 and Th2 effector cytokines immediately after stimulation and also express IL-4 in addition to IFN-γ under the Th1 differentiation condition. In the present study, we investigated the capability of T-CD4 T cells to become IL-17-producing cells. We found that T-CD4 T cells express reduced IL-17 under Th17-inducing conditions. T-CD4 T cells express very low levels of receptor for TGF-β and IL-21 that are essential to induce IL-17 expression. In addition, the induction of RORγt, a key transcription factor for IL-17 gene expression, was compromised in T-CD4 T cells under Th17 skewing conditions and ectopic expression of RORγt restored IL-17 expression. The defect of IL-17 and RORγt expression in T-CD4 T cells is cell intrinsic and not due to effects of a secreted factor. Thus, the developmental pathway of CD4 T cells in the thymus plays a critical role in controlling an immune response by suppressing the generation of the Th17 lineage.

Original languageEnglish (US)
Pages (from-to)1262-1268
Number of pages7
JournalMolecular Immunology
Volume47
Issue number6
DOIs
StatePublished - Mar 1 2010

Keywords

  • Cytokines
  • IL-17
  • IL-21
  • T cell signaling
  • T-CD4
  • TGF-b

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

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