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- W2007369871 abstract "Rationale: Asthma is a chronic airway inflammation caused by overproduction of Th2 cytokines. IL-27 has been shown to inhibit differentiation of naive CD4+ cells into Th2 cells in mice.However, it is not clear whether IL-27 can inhibit Th2 cell differentiation in asthmatic patients. Methods: Purify CD4+ T cells from human PBMC and mice spleen were cultured under Th2 or Th2 + IL-27 conditions. IL-4 and IFN-gamma were detected by ELISA. IL-27R and p-STATs were determined by qRT-PCR and Western blot respectively. Results: human IL-27 suppressed Th2 differentiation in healthy subjects (p=0.006), but failed to do so in asthmatics (p=0.064). The suppressive effect of IL-27 on Th2 development was independent of IFN-r, IL-10 and T-bet. However studies with STAT1-knockout mice showed that this inhibitory effect of IL-27 was STAT1-dependent. IL-27 resistance to Th2 differentiation in asthmatics was not dependent on impairment of IL-27R.We further found that Th2-inducing conditions could induce resistance to IL-27 in a dose-dependent manner and IL-4 is the most critical factor. Although IL-2 is imperative in Th2 cell priming, it does not contribute to induction of the IL-27 resistance. We demonstrated that high dose of IL-4 treatment resulted in impairment of STAT1 phosphorylation, but not STAT3 or STAT4 phosphorylation. Conclusions: IL-27 suppresses the development of Th2 immune response in both mice and human, which is STAT1-dependant, but independent of IFN-r, IL-10 and T-bet. CD4+ T cells from asthmatics developed resistance to IL-27-mediated inhibition. IL-4 induced resistance to IL-27-mediated inhibition by impairing STAT1 signaling." @default.
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- W2007369871 date "2012-05-01" @default.
- W2007369871 modified "2023-09-27" @default.
- W2007369871 title "IL-4 Induces Th2 Cells To Rresist The IL-27 Counterregulation By Downregulating STAT1 And STAT2 Phosphorylation" @default.
- W2007369871 doi "https://doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1412" @default.
- W2007369871 hasPublicationYear "2012" @default.
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