title: The regulation and role of c-FLIP in human Th cell differentiation.
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 Th cells.
authors.affiliation: Turku 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.
authors.forename: Minna K
authors.initials: MK
authors.lastname: Kyläniemi
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
authors.forename: Riina
authors.initials: R
authors.lastname: Kaukonen
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Myllyviita
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
authors.forename: Omid
authors.initials: O
authors.lastname: Rasool
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
mesh_terms: D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D017931:DNA Primers; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D015847:Interleukin-4