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 language | English (US) |
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Pages (from-to) | 167-176 |
Number of pages | 10 |
Journal | Mucosal Immunology |
Volume | 6 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2013 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology