IL17A impairs blood–testis barrier integrity and induces testicular inflammation

• Published in: Cell and tissue research Vol. 358; no. 3; pp. 885 - 898
• Main Authors: Pérez, Cecilia Valeria, Pellizzari, Eliana Herminia, Cigorraga, Selva Beatriz, Galardo, María Noel, Naito, Munekazu, Lustig, Livia, Jacobo, Patricia Verónica
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.12.2014; Springer Berlin Heidelberg; Springer; Springer Nature B.V
• Subjects: Analysis; Animals; apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; biotin; Blood-Testis Barrier - metabolism; Blood-Testis Barrier - pathology; cell adhesion; Cell adhesion & migration; cell culture; chemoattractants; Chemokine CCL2 - metabolism; Claudins - metabolism; Cytokines; Electric Impedance; electrical resistance; gene expression; germ cells; Germ Cells - drug effects; Germ Cells - pathology; Human Genetics; Immune system; in vitro studies; Inflammation; Inflammation - metabolism; Inflammation - pathology; Interleukin-17 - metabolism; Lymphocytes - metabolism; macrophages; Macrophages - metabolism; Male; messenger RNA; Molecular Medicine; Occludin; occludins; orchitis; Orchitis - metabolism; Orchitis - pathology; Permeability; Proteomics; rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptors, CCR2 - metabolism; Receptors, Interleukin-17 - metabolism; recruitment; Regular Article; Reproductive system; RNA; seminiferous tubules; Sertoli cells; Sertoli Cells - metabolism; tight junctions; Tight Junctions - metabolism; Up-Regulation - drug effects; Vascular Cell Adhesion Molecule-1 - metabolism; Blood–testis barrier; Testicular inflammation; Sertoli cells; IL17A; Cell adhesion molecules
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-014-1995-5

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 protein Ccl2, its receptor Ccr2 and the vascular cell adhesion molecule Vcam1. 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.