Abstract
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.
Highlights
The family of interferon-inducible transmembrane (Ifitm/Fragilis) genes (Ifitm1, 2, 3, 5, and 6) encode homologous proteins that have recently been shown to confer cellular resistance to viruses [1]
We found significant increase in expression in the IfitmF–/– CD4+ T cells compared to WT of Th1-associated genes such as Cd84, Cd226, and Cd154 and Il27ra, which signals for Stat1 activation during early Th1 differentiation [19,20,21], whereas there was no difference in expression levels of the master Th1 transcription factor Tbx21 between genotypes (Fig. 1F)
Much recent research on IFN-inducible transmembrane · mediastinal lymph nodes (mLN) (IFITM) proteins has focused on their role in cellular resistance to viral infections, but their function in CD4+ T cells during the adaptive immune response is less well understood
Summary
The family of interferon-inducible transmembrane (Ifitm/Fragilis) genes (Ifitm , and 6) encode homologous proteins that have recently been shown to confer cellular resistance to viruses [1]. Their promoters have one or more interferon stimulated response elements (ISRE), which make them responsive to IFNs [2]. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
