FIGURE 19.17.

Intercompartmental interactions regulating steroidogenesis, spermatogenesis and immune responses in the adult testis.

Within the seminiferous epithelium, the Sertoli cell supports and regulates spermatogenesis, through production of cytokines, including interleukin-1α (IL1α), IL6, and activin. Production of these cytokines is stimulated by the presence of the spermatogenic cells. Spermatogenic cells also produce tumor necrosis factor (TNF) and NO, which regulate Sertoli cell functions, such as the maintenance of the blood–testis barrier. Sertoli cells possess a number of immunosuppressive activities, which include expression of indoleamine 2,3-dioxygenase (IDO), HLA-G, programmed death-1 ligand-1 (PD-L1), and FAS ligand (FASL). Spermatogenic antigens released from the seminiferous epithelium, together with local production of immunoregulatory molecules, including IL10, transforming growth factor-β (TGFβ), activin, prostaglandins/leukotrienes (PG/LT), and lyso-glycerophosphatidylcholines (lyso-GPCs), create an environment that promotes tolerogenic responses (alternatively activated resident macrophages, Treg cells) and innate immunity (NK cells, cytotoxic T cell), while inhibiting cell-mediated immunity (helper T cells). Leydig cells are responsible for recruiting macrophages into the testis and may have further immunomodulatory actions through production of androgens, and other molecules with immunoregulatory actions, such as prostaglandins (PGs). DC, dendritic cells; NK, NK cells: CTL, cytotoxic lymphocytes; Th, helper T cells; Treg, regulatory T cells.