title: Testosterone replacement effectively inhibits the development of experimental autoimmune orchitis in rats: evidence for a direct role of testosterone on regulatory T cell expansion.
abstract: Despite the immune-privileged status of the male genital tract, infection and inflammation of the male genital tract are important etiological factors in male infertility. A common observation in clinical and experimental orchitis as well as in systemic infection and inflammation are decreased levels of testosterone. Emerging data point to an immunosuppressive role of testosterone. In our study, we substituted testosterone levels in experimental autoimmune orchitis (EAO) in rat by s.c. testosterone implants. EAO development was reduced to 17% when animals were treated with low-dose testosterone implants (3 cm long, EAO+T3) and to 33% when rats were supplied with high-dose testosterone implants (24 cm, EAO+T24) compared with 80% of animals developing disease in the EAO control group. In the testis, testosterone replacement in EAO animals prevented the accumulation of macrophages and significantly reduced the number of CD4(+) T cells with a strong concomitant increase in the number of regulatory T cells (CD4(+)CD25(+)Foxp3(+)) compared with EAO control. In vitro testosterone treatment of naive T cells led to an expansion of the regulatory T cell subset with suppressive activity and ameliorated MCP-1-stimulated chemotaxis of T lymphocytes in a Transwell assay. Moreover, expression of proinflammatory mediators such as MCP-1, TNF-α, and IL-6 in the testis and secretion of Th1 cytokines such as IFN-γ and IL-2 by mononuclear cells isolated from testicular draining lymph nodes were decreased in the EAO+T3 and EAO+T24 groups. Thus, our study shows an immunomodulatory and protective effect of testosterone substitution in the pathogenesis of EAO and suggests androgens as a new factor in the differentiation of regulatory T cells.
authors: Department of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 35385 Giessen, Germany.
authors: Monika
authors: M
authors: Fijak
authors: Eva
authors: E
authors: Schneider
authors: Jörg
authors: J
authors: Klug
authors: Sudhanshu
authors: S
authors: Bhushan
authors: Holger
authors: H
authors: Hackstein
authors: Gerhard
authors: G
authors: Schuler
authors: Malgorzata
authors: M
authors: Wygrecka
authors: Jörg
authors: J
authors: Gromoll
authors: Andreas
authors: A
authors: Meinhardt
mesh_terms: D000728:Androgens / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008856:Microscopy, Fluorescence; D009920:Orchitis / Q000188:drug therapy / Q000276:immunology*; D051381:Rats; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013739:Testosterone / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000728:Androgens; D016207:Cytokines; D013739:Testosterone