Sertoli cell-specific deletion of the androgen receptor compromises testicular immune privilege in mice.

Document Type

Article

Publication Date

8-2011

JAX Source

Biol Reprod 2011 Aug; 85(2):254-60.

PMID

21543771

Volume

85

Issue

2

First Page

254

Last Page

260

ISSN

1529-7268

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.

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