title: Inhibition of JAK/STAT pathway restrains TSLP-activated dendritic cells mediated inflammatory T helper type 2 cell response in allergic rhinitis.
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.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, People's Republic of China.|Senna Otolaryngology Head and Neck Surgery Hospital, No. 808, Cuihua Road, Yanta District, Xi'an, 710061, Shaanxi, People's Republic of China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, XiangYa Hospital, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, People's Republic of China.|Senna Otolaryngology Head and Neck Surgery Hospital, No. 808, Cuihua Road, Yanta District, Xi'an, 710061, Shaanxi, People's Republic of China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, People's Republic of China. liqiao_xa@21cn.com.|Senna Otolaryngology Head and Neck Surgery Hospital, No. 808, Cuihua Road, Yanta District, Xi'an, 710061, Shaanxi, People's Republic of China. liqiao_xa@21cn.com.
authors.forename: Li
authors.initials: L
authors.lastname: Qiao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D053612:Janus Kinases / Q000276:immunology*; D051379:Mice; D065631:Rhinitis, Allergic / Q000276:immunology* / Q000473:pathology; D050791:STAT Transcription Factors / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D050791:STAT Transcription Factors; D053612:Janus Kinases; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: Allergic rhinitis; Dendritic cells; JAK/STAT; OX40L