Table 1.
Selected immunomodulatory factors expressed by Sertoli cells.
| Cytokine | Protects from | Immune function | Function in testes | Ref |
|---|---|---|---|---|
| Gal-1 | Immune system | Encourages development and maintenance of tolerogenic dendritic cells | May play a role in spermatogenesis and spermiation | (49, 50) |
| IGF-1 | Immune system | Decreases production of proinflammatory cytokines IL-1β, TNF-α, and leukocyte chemoattractants | Cell development, proliferation, and function | (51–53) |
| IDO | Immune system | Suppresses effector T cell functions, induces tolerogenic APCs and Tregs | Testicular immune tolerance, protects against autoimmune orchitis | (54, 55) |
| TGF-β | Immune system | Develops immune tolerance to self and generates Tregs | Regulates Sertoli cell TJ, encourages germ cell differentiation and proliferation | (56, 57) |
| Activin A | Immune system | Aids in Th2 and Treg induction | Regulates FSH production and Sertoli cell and germ cell growth | (58–61) |
| SERPINA3N | Immune system | Inhibits granzyme B and CTL-mediated killing | Prevents apoptosis, may facilitate migration of developing germ cells | (62–64) |
| SERPINB9 | Immune system | Protects cells from lymphocyte-secreted granzyme B | Anti-apoptotic cell survival factor | (65–70) |
| IL-6 | Immune system and Infection | Increases production of acute phase proteins, platelet, and antibody production; and generates effector T cells; generates Tregs in the presence of TGF-β, retinoic acid, and dendritic cells | Mediates spermatogenesis signaling cascades | (71, 72) |
| IL-1β | Infection | Increases expression of proinflammatory cytokines TNF-α and IL-6, generates Th17 cells | Spermatogenesis maintenance | (73) |
| TNF-α | Infection | Inflammatory cytokine that leads to apoptosis or necrosis of cells | Promotes cell survival; regulates BTB with TGF- β in spermatogenesis to allow migration of spermatocytes | (74–76) |
| β-defensin | Infection | Antimicrobial peptide | Protects seminiferous tubules from infection | (77, 78) |
| IFN-γ | Infection | Activates effector immune cells like macrophages to clear viral infections; increase PKR expression, polarize T cells to Th1 cells | Regulates Sertoli cell survival and function, protects seminiferous tubules from viral infection | (79, 80) |
| PKR | Infection | Inhibits translation of viral mRNA, stimulates apoptosis of virus-infected cells, increases expression of IFN-γ | Protects seminiferous tubules from viral infection | (81, 82) |