IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation
The interferon‐inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4+ Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild‐type (WT) CD4+ T cells. On activation, Ifitm3 was downregulated a...
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Veröffentlicht in: | European journal of immunology 2019-01, Vol.49 (1), p.66-78 |
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Zusammenfassung: | The interferon‐inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4+ Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild‐type (WT) CD4+ T cells. On activation, Ifitm3 was downregulated and Ifitm2 was upregulated. Resting Ifitm‐family‐deficient CD4+ T cells had higher expression of Th1‐associated genes than WT and purified naive Ifitm‐family‐deficient CD4+ T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited.
Ifitm‐family‐deficient mice, but not Ifitm3‐deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL‐27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology.
The interferon‐inducible transmembrane (IFITM) proteins influence Th1/Th2 polarization and promote Th2 differentiation. In absence of IFITM proteins, CD4 T‐cell differentiation is biased towards Th1, by a cell‐autonomous mechanism. IFITM‐deficient mice are less susceptible to induction of allergic airways disease by inhibition of the Th2 response and inflammation. |
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ISSN: | 0014-2980 1521-4141 |
DOI: | 10.1002/eji.201847692 |