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The regulation and role of c-FLIP in human Th cell differentiation.

Kyläniemi MK1, Kaukonen R2, Myllyviita J2, Rasool O2, Lahesmaa R2.

PLoS One. 2014 Jul 14;9(7):e102022.

1Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; National Doctoral Programme in Informational and Structural Biology, Åbo Akademi University, Turku, Finland and

2Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.

 

Abstract

 The early differentiation of T helper (Th) cells is a tightly controlled and finely balanced process, which involves several factors including cytokines, transcription factors and co-stimulatory molecules. Recent studies have shown that in addition to the regulation of apoptosis, caspase activity is also needed for Th cell proliferation and activation and it might play a role in Th cell differentiation. The isoforms of the cellular FLICE inhibitory protein (c-FLIP) are regulators of CASPASE-8 activity and the short isoform, c-FLIPS, has been shown to be up-regulated by IL-4, the Th2 driving cytokine. In this work, we have studied the expression and functional role of three c-FLIP isoforms during the early Th cell differentiation. Only two of the isoforms, c-FLIPS and c-FLIPL, were detected at the protein level although c-FLIPR was expressed at the mRNA level. The knockdown of c-FLIPL led to enhanced Th1 differentiation and elevated IL-4 production by Th2 cells, whereas the knockdown of c-FLIPS diminished GATA3 expression and IL-4 production by Th2 cells. In summary, our results provide new insight into the role of c-FLIP proteins in the early differentiation of human Thcells.

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