Induction of Th17 differentiation by corneal epithelial-derived cytokines.
Induction of Th17 differentiation by corneal epithelial-derived cytokines.
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DOI：
10.1002/jcp.21926
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发表时间：
2010-01
影响因子：
5.6
通讯作者：
Li, De-Quan
中科院分区：
文献类型：
--
作者：
Zheng, Xiaofen;Bian, Fang;Ma, Ping;De Paiva, Cintia S.;Stern, Michael;Pflugfelder, Stephen C.;Li, De-Quan
本研究旨在探讨上皮源性细胞因子在Th17分化中的潜在作用。用5种诱导细胞因子的不同组合处理小鼠的CD4+T细胞，或人角膜上皮细胞(HCECs)暴露于各种刺激的条件培养液中，评估Th17的诱导作用。采用实时定量聚合酶链式反应检测Th17相关分子IL-17A、IL-17F、IL-22、CCL-20和STAT3的表达，用实时定量聚合酶链式反应检测产生IL-17的T细胞的数量，用细胞因子免疫珠法和ELISPOT法检测Th17细胞的分化。IL-23在转化生长因子-β-1+IL-6存在时对Th17细胞的扩增作用最强，IL-1β在转化生长因子-β-1+IL-6+IL-23存在时对Th17细胞的扩增作用最强。这些诱导细胞因子在高渗介质(450mOsM)、微生物成分(PolyI：C、鞭毛蛋白、R837和其他TLR配体)和肿瘤坏死因子-α的刺激下被显著刺激。有趣的是，当与PolyI：C或肿瘤坏死因子-α刺激的人脐静脉内皮细胞条件培养液孵育时，CD4+T细胞表现出IL-17A、IL-17F、IL-22、CCL-20和STAT3mRNA水平升高，培养上清液中IL-17蛋白表达增加，产生IL-17的T细胞(Th17细胞)数量增加。这些发现首次证明，角膜上皮细胞产生的细胞因子可以促进Th17的分化，这些细胞因子暴露在高渗、微生物和炎症刺激下。
This study was to explore a potential role of epithelium-derived cytokines in Th17 differentiation. Th17 induction was evaluated by murine CD4+ T cells treated with different combinations of 5 inducing cytokines, or conditioned media of human corneal epithelial cells (HCECs) exposed to a variety of stimuli. Th17 differentiation was determined by measuring Th17 associated molecules, IL-17A, IL-17F, IL-22, CCL-20 and STAT3 at mRNAand protein levels, and numbers of IL-17-producing T cells by real-time PCR, and cytokine immunobead and ELISPOT assays, respectively. IL-23 was the strongest inducer for expanding Th17 cells in the presence of TGF-β1+IL-6; and IL-1β was the strongest Th17 amplifier in the presence of TGF-β1+IL-6+IL-23. These inducing cytokines were found to be significantly stimulated in HCECs challenged by hyperosmotic media (450 mOsM), microbial components (polyI:C, flagellin, R837 and other TLR ligands) and TNF-α. Interestingly, when incubated with conditioned media of HCECs irritated by polyI:C or TNF-α, CD4+ T cells displayed increased mRNA levels of IL-17A, IL-17F, IL-22, CCL-20 and STAT3, increased IL-17 protein in the supernatant, and increased numbers of IL-17-producing T cells (Th17 cells). These findings demonstrate for the first time that Th17 differentiation can be promoted by cytokines produced by corneal epithelium that are exposed to hyperosmotic, microbial and inflammatory stimuli.
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影响因子：
30.5
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