Th22细胞因子协同促进小鼠输卵管上皮细胞抗沙眼衣原体感染体外研究

目的体外研究Th22细胞因子(IL-22、TNF-α)在小鼠输卵管上皮细胞抵抗沙眼衣原体感染过程中的作用。方法体外培养Th22细胞,ELISA检测Th22上清中细胞因子含量及其对体外培养的小鼠输卵管上皮细胞(MOECs)表达Th1趋化因子、抗菌肽的影响;Transwell实验检测MOECs上清对Th1细胞的趋化能力;分别用免疫荧光法、PCR及7-乙氧基试卤灵(7-ethoxyresrufin, 7-ER)法检测Th22上清对输卵管上皮细胞抑制Chlamydia trichomatis (Ct)能力、促进胰岛再生源蛋白3g(regenerating islet-derived protein-3g,Reg3g) Reg3g表达及细胞活性的影响。结果Th22细胞以分泌IL-22、TNF-α为主。Th22上清可诱导MOECs表达Th1细胞趋化因子CXCL9/10/11及抗菌肽mBD-2表达,活化MOECs对Th1细胞具有趋化作用并抑制Ct生长。同时,Th22上清可促进MOECs Reg3g表达及增强其活性。结论Th22细胞因子能增强MOECs介导的天然免疫功能,促进其损伤修复,在Ct及其它性传播疾病中可能发挥重要作用。

Potential protective role of the Th22 cytokines against Chlamydia trichomatis infection in genital tract

Th22 cells are a novel class of leukocytes characterized by the secretion of both IL-22 and TNF-α. Th22 cells have little or no direct impact on other immune cells, but exert selective effects on epithelia. It is not known, however, whether Th22 cells play a role in genital mucosal immunity. Here, we demonstrate that IL-22 and TNF-α synergistically induce several immunomodulatory molecules, such as the antimicrobial peptide mBD-2 (murine β-defensin 2) and the antimicrobial chemokines CXCL-9, -10, and -11 in primary murine oviduct epithelial cells (MOECs). The induction of innate immunity is relevant in an in vitro infection model, in which MOECs stimulated with Th22 cell supernatants effectively inhibit the growth of Chlamydia trichomatis and maintain the survival of the epithelia compared with untreated control. In summary, we demonstrate that the Th22 cell cytokines IL-22 and TNF-α play important roles in genital tract infection. The potential for Th22 cell cytokines to modulate innate immune mediators may lead to the development of new topical agents to treat and/or prevent immune-mediated STDs.