IL17A impairs blood–testis barrier integrity and induces testicular inflammation
IL17A impairs blood–testis barrier integrity and induces testicular inflammation
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DOI：
10.1007/s00441-014-1995-5
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发表时间：
2014-09
影响因子：
3.6
通讯作者：
C. Pérez;E. Pellizzari;S. Cigorraga;M. Galardo;M. Naito;L. Lustig;P. Jacobo
中科院分区：
文献类型：
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作者：
C. Pérez;E. Pellizzari;S. Cigorraga;M. Galardo;M. Naito;L. Lustig;P. Jacobo
实验性自身免疫性睾丸炎是研究睾丸炎症和生殖细胞/免疫细胞相互作用的有用模型。据报道，Th17细胞及其标志性细胞因子IL17A参与了自身免疫性炎的发生。本研究旨在探讨IL17A在大鼠睾丸中的致病作用。体外实验分析IL17A对支持细胞紧密连接的影响。正常大鼠Sertoli细胞加入IL17A后，跨上皮电阻值显著降低，occludin和claudin 11表达减少，分布重新分布，改变了Sertoli细胞紧密连接屏障。睾丸内注射重组大鼠IL17A的1μg可引起血-睾丸屏障通透性增加，表现为曲细精管腺腔内有生物素示踪剂存在，occludin和claudin 11移位。结果表明，IL17A可引起生精小管局灶性炎症细胞浸润和邻近曲细精管的生殖细胞脱落。此外，还观察到TUNEL+凋亡生殖细胞增多。注射IL17A后，炎性ED1+巨噬细胞是主要的间质细胞。这与单核细胞趋化蛋白Ccl2、其受体Ccr2和血管细胞黏附分子Vcam1的mRNA表达增加有关。总体而言，结果提示IL17A在睾丸炎症的发生发展中起着相关的作用，促进免疫细胞向睾丸间质募集，并导致血-睾丸屏障功能的损害。
Experimental autoimmune orchitis is a useful model for studying testicular inflammation and germ/immune cell interactions. Th17 cells and their hallmark cytokine IL17A were reported to be involved in the development of autoimmune orchitis. The aim of the present work is to investigate the pathogenic role of IL17A in rat testis. In vitro experiments were performed in order to analyze effects of IL17A on Sertoli cell tight junctions. The addition of IL17A to normal rat Sertoli cell cultures induced a significant decline in transepithelial electrical resistance and a reduction of occludin expression and redistribution of occludin and claudin 11, altering the Sertoli cell tight junction barrier. Intratesticular injection of 1 μg of recombinant rat IL17A to Sprague–Dawley rats induced increased blood–testis barrier permeability, as shown by the presence of biotin tracer in the seminiferous tubule adluminal compartment, and delocalization of occludin and claudin 11. Results showed that IL17A induced focal inflammatory cell infiltration in the interstitium and germ cell sloughing in adjacent seminiferous tubules. Moreover, an increase in TUNEL+ apoptotic germ cells was also observed. Inflammatory ED1+ macrophages were the main population infiltrating the interstitium following IL17A injection. This correlated with an increase in mRNA expression of the monocyte chemoattractant proteinCcl2, its receptorCcr2and the vascular cell adhesion moleculeVcam1. Overall results suggest a relevant role of IL17A in the development of testicular inflammation, facilitating the recruitment of immune cells to the testicular interstitium and inducing impairment of blood–testis barrier function.