The role of the testicular microenvironment in inducing a testis-specific phenotype of testicular macrophages

Abstract

Testicular macrophage (TM) is the major immune cell population in the testis, and displays a critical function in spermatogenesis together with Leydig cells: hormone production is TM-dependent; Sperm with neo-antigens are protected from immune attack. Resident macrophages with specific profiles have been shown to be induced by local microenvirnmental factors, like microglia in the brain, is maintained by IL-34, and regulated by TGF-β through the downstream transcription factors, SMADs. 25-hydrocholesterol (25HC) and interferon β (IFN-β) can be produced by macrophages and are highly expressed in the testis. IRF7, the master transcription factor of IFN-β, is also shown to balance the macrophage functions and is highly expressed in TM. Our study finds that 25HC displays dual inflammatory functions depend on the initial activation by M-CSF, which is also regulated by IRF7. We compare all male reproductive organs between Irf7-/- and wild type mice, and find that IRF7 is important to repress the expression of MHC II in most of the resident macrophages. Of note, only in the testis, the survival of macrophage shows close relation with IRF7. In conclusion, we relate metabolism of cholesterol with inflammatory regulations in the male reproductive organs. M-CSF in the testis displays as an initial factor to induce high levels of 25HC and IRF7. The high level of IRF7 can repress the expression of MHC II, and the high concentration of 25HC shows anti-inflammatory functions,which together form the specific TM profile.