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  • Title: Inhibition of JAK/STAT pathway restrains TSLP-activated dendritic cells mediated inflammatory T helper type 2 cell response in allergic rhinitis.
    Author: Shi Z, Jiang W, Wang M, Wang X, Li X, Chen X, Qiao L.
    Journal: Mol Cell Biochem; 2017 Jun; 430(1-2):161-169. PubMed ID: 28214951.
    Abstract:
    Thymic stromal lymphopoietin (TSLP) has recently been implicated as a key molecule for initiating allergic rhinitis (AR) at the cell-dendritic cell (DC) interface. Previous studies demonstrated that TSLP activated DCs to express more OX40 ligand (OX40L), which is associated with the initiation of T helper type 2 (Th2) cell responses. STAT phosphorylation has been reported to be promoted by TSLP. Thus, we investigated if the JAK/STAT pathway inhibitor CYT387 could affect TSLP-DC-mediated Th2 cell response in naive T cell and AR mice model. Western blot showed that the levels of phosphorylated JAK1, JAK2, STAT1, STAT3, and STAT5 were increased in TSLP-DCs, which can be offset by CYT387. Flow cytometry indicated that CYT387 had obviously down-regulated the surface maturation co-stimulatory molecules (CD11c, CD80, CD86, and MHCII) in DCs, which were increased by TSLP. Moreover, CYT387 markedly reduced the ability of TSLP-DCs to promote the differentiation of naive CD4+ T cells into IL-4-expressing Th2 cells. The histological examination showed that the CYT387-treated group showed less epithelial disruption, epithelial cell proliferation, and reduced eosinophil infiltration compared with AR group. Western blot and RT-PCR demonstrated that the expression of OX40L was increased in AR mice, but that it was decreased by CYT387. Furthermore, CYT387 treatment resulted in the reduction of IL-4 and IL-5 expression and increased IFN-γ level in AR mice, which was consistent with the levels of intracellular cytokine in Th2 cell. In conclusion, we suggest that blockading the JAK/STAT pathway restrains inflammatory Th2 cell response induced by TSLP-DCs in AR.
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