IL-23 receptor regulation by Let-7f in human CD4+ memory T cells

Zhaoxia Li, Feng Wu, Steven R. Brant, John H. Kwon

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

CD4+ memory T cells include the Th17 cell population, which has been shown to be implicated in autoimmune and inflammatory diseases. These memory T cells express higher IL-23R and produce more IL-17 compared with their naive counterparts. However, the molecular mechanisms that regulate IL-23R expression in human T cells are not completely understood. MicroRNAs play important roles in a wide range of biological events through posttranscriptional suppression of target mRNAs. In this article, we provide evidence that a specific microRNA, Let-7f, inhibits IL-23R expression in human CD4+ memory T cells. Endogenous expression of Let-7f in memory T cells is significantly lower when compared with naive T cells, and Let-7f blocks IL-23R expression through its complementary target sequence within 3′ untranslated region of target gene. Furthermore, exogenous transfection of a Let-7f mimic into memory T cells results in downregulation of IL-23R and its downstream cytokine, IL-17. Our findings reveal a novel mechanism in regulating the IL-23/IL-23R pathway and subsequent downstream IL-17 production, which may provide novel therapeutics for human inflammatory and autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)6182-6190
Number of pages9
JournalJournal of Immunology
Volume186
Issue number11
DOIs
StatePublished - Jun 1 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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