Tim4-Tim1 Interaction Modulates Th2 Pattern Inflammation Through Enhancing Sirt1 Expression
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE(2017)
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 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.
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关键词
allergy, T-cell immunoglobulin and mucin domain 4, T-cell immunoglobulin and mucin domain 1, T helper 2, silent information regulator 1
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