TGF-β conditions intestinal T cells to express increased levels of miR-155, associated with down-regulation of IL-2 and itk mRNA

L. M. Das, M. D.L.A. Torres-Castillo, T. Gill, A. D. Levine

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Transforming growth factor (TGF)-β, is an immunosuppressive cytokine that inhibits T-cell activation. We hypothesized that TGF-β mediates its immunoinhibitory effects by modulation of micro RNA (miRNA)-155 (miR-155). Interleukin (IL)-2 and interferon-γ are down-regulated by TGF-β in activated CD4 peripheral blood T cells and lamina propria T cells (LPT), but miR-155 is upregulated ninefold specifically in LPT. Consequently, this study focuses on the role of TGF-β-enhanced miR-155 on LPT immune responses. TGF-β induces miR-155 in both freshly isolated and LPT lymphoblasts, whereas other inducible miRNAs are not regulated by TGF-β. Using MAMI bioinformatics database, we determined that inducible T-cell kinase (itk) is a functional target of miR-155 that exhibits an inverse mRNA response to that of miR-155. To determine experimentally that miR-155 regulates itk, transfection experiments were performed that demonstrated miR-155 overexpression decreased itk and IL-2 mRNA, whereas antagonism of miR-155 restored both mRNAs in activated cells. These findings describe a TGF-β-dependent function for miR-155 in modulating cytokine and T-cell immune responses in the gut.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalMucosal Immunology
Volume6
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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