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TIM4-TIM1 interaction modulates Th2 pattern inflammation through enhancing SIRT1 expression.

Int. J. Mol. Med.2017 Nov;40(5):1504-1510. doi:10.3892/ijmm.2017.3150. Epub 2017 Sep 25
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摘要


Skewed T helper 2 (Th2)‑cell polarization plays a critical role in the pathogenesis of allergic inflammations; however, the underlying mechanisms require further elucidation. The aim of the present study was to investigate the mechanisms through which the interaction between T‑cell immunoglobulin and mucin domain (TIM)4 and TIM1 regulates the expression of silent information regulator 1 (SIRT1) in Th2 cells, and the role of SIRT1 in Th2‑cell polarization during nasal allergic inflammation. The results demonstrated that TIM4 expression by splenic dendritic cells was increased in mice with allergic rhinitis, and the TIM4̸TIM1 interaction promoted CD4+ T cells to express SIRT1 during allergic inflammation via enhancing phosphoinositide 3‑kinase/Akt phosphorylation. SIRT1 then facilitated CD4+ T‑cell proliferation through downregulating the expression of Fas ligand, caspase-3 and p53 in mice with nasal allergic inflammation. In conclusion, the interaction of TIM4̸TIM1 was found to promote Th2‑cell proliferation through enhancing SIRT1 expression in mice with nasal allergic rhinitis.

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