TGF-β conditions intestinal T cells to express increased levels of miR-155, associated with down-regulation of IL-2 and itk mRNA.
TGF-β conditions intestinal T cells to express increased levels of miR-155, associated with down-regulation of IL-2 and itk mRNA.
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Transforming Growth Factor (TGF)-β, is an immunosuppressive cytokine that inhibits T cell activation. We hypothesized that TGF-β mediates its immuno-inhibitory effects by modulation of micro (mi)RNA-155. IL-2 and IFN-γ are down-regulated by TGF-β in activated CD4 peripheral blood T cells (PBT) and lamina propria T cells (LPT), but miR-155 is up-regulated 9-fold 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 while 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.
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影响因子：
15.3
作者：
Fahlén, L;Read, S;Gorelik, L;Hurst, SD;Coffman, RL;Flavell, RA;Powrie, F
通讯作者：
Powrie, F
DOI：
10.4049/jimmunol.0803560
发表时间：
2009-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Munitz A;Rothenberg ME
通讯作者：
Rothenberg ME
DOI：
10.4049/jimmunol.1002218
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Divekar AA;Dubey S;Gangalum PR;Singh RR
通讯作者：
Singh RR
影响因子：
5.3
作者：
Kong, William;Yang, Hua;Cheng, Jin Q.
通讯作者：
Cheng, Jin Q.
影响因子：
32.4
作者：
Lu, Li-Fan;Thai, To-Ha;Calado, Dinis Pedro;Chaudhry, Ashutosh;Kubo, Masato;Tanaka, Kentaro;Loeb, Gabriel B.;Lee, Hana;Yoshimura, Akihiko;Rajewsky, Klaus;Rudensky, Alexander Y.
通讯作者：
Rudensky, Alexander Y.