Roles Of Axl And Mer Receptor In Regulating Autoimmune Orchitis And Mechanism Underlying Poly(I:C)-induced Orchitis

The mammalian testis is an immune privilege site. Growing evidence suggests that both systemic immune tolerance and local immunosuppression are involved in controlling the immune privilege status in the testis. However, the mechanisms underlying the testicular immune privilege remain to be fully understood. We recently demonstrated that Tyro3, Axl and Mer (TAM) receptor tyrosine kinases triple knockout (TAM-/-) mice display disruption of immune homeostasis in the testis. In this study, we further investigated the roles of individual Tyro3, Axl and Mer receptor tyrosine kinases in regulating the testicular immune privilege using TAM single mutant and any combination of double mutant (AT-/-, AM-/-, TM-/-) mice. We found that AM-/-mice were more susceptible to testicular autoimmune induction. Immunization of AM-/-mice with testicular homogenate, caused experimental autoimmune orchitis (EAO) in all animals, characterized by the accumulation of macrophages in the testis, the generation of autoantibodies against spermatic antigens and the evident testicular damages. By contrast, all single knockout and AT-/-, TM-/-mice developed mild EAO after immunization with testicular homogenates, which are comparable with wild-type (WT) control. The results suggest that Axl and Mer play important role in regulating testicular immune privilege.Systemic viral infection may impair spermatogenesis, thus resulting in male infertility. It is unclear that how the innate immune responses induced by viral infection impaire spermatogenesis. To understand the mechanism underlying impaired spermatogenesis due to the viral infections, we examined the defects of intraperitoneal injection of polyinosinic-polycytidylic acid [Poly(I:C)] on spermatogenesis. We found that the intraperitoneal injection of Poly(I:C) induces apoptosis of germ cells mainly through the elevation of TNFa. These results suggest that TNFa may be a therapeutic target for the testicular inflammation induced by systemic viral infection.