title: Sertoli cell-specific deletion of the androgen receptor compromises testicular immune privilege in mice.
abstract: In the mammalian testis, meiotic and postmeiotic germ cell antigens are granted immune privilege. Both local immune suppression and specialized intercellular junctions between somatic Sertoli cells have been proposed to contribute to a highly restricted and effective blood-testis barrier (BTB) that helps maintain tolerance to germ cell antigens. Several studies have suggested that androgens play a role in immune suppression, although direct evidence for this is lacking. We previously reported that Sertoli cell-specific ablation of the androgen receptor (Ar) decreases expression of Cldn3, an androgen-regulated gene and component of Sertoli cell tight junctions, and increases the permeability of the BTB to biotin, a small-molecular-weight tracer. The physiological consequences of Sertoli cell-specific Ar (S-Ar) ablation on immune privilege are unknown. Here we show that in the testes of S-Ar mutant mice, the ultrastructure of Sertoli cell tight junctions is defective and testicular IgG levels are elevated. The interstitium of S-Ar mutant testes becomes populated with macrophages, neutrophils, plasma cells, and eosinophils, and serum samples of mutant mice contain antibodies against germ cell antigens. Together, these results suggest that Sertoli cell-specific deletion of the androgen receptor results in loss of testicular immune privilege. Suppressed levels of androgen signaling may be a contributing factor in idiopathic male infertility.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Meng
authors.forename: Anne R
authors.initials: AR
authors.lastname: Greenlee
authors.forename: Chloe J
authors.initials: CJ
authors.lastname: Taub
authors.forename: Robert E
authors.initials: RE
authors.lastname: Braun
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies; D001814:Blood-Testis Barrier / Q000502:physiology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D005854:Germ Cells / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D051379:Mice; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism* / Q000648:ultrastructure; D013737:Testis / Q000276:immunology*; D019108:Tight Junctions / Q000648:ultrastructure
chemical_list: D000941:Antigens; D001323:Autoantibodies; D007074:Immunoglobulin G; D011944:Receptors, Androgen