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

Abstract

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 TIM4?TIM1 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 TIM4?TIM1 was found to promote Th2-cell proliferation through enhancing SIRT1 expression in mice with nasal allergic rhinitis.