Shielding from Complement Attack! Sertoli Cells Survive Complement Activation and Express Anti-Inflammatory Genes 3158

Abstract Description Testicular Sertoli cells (SC) provide an immunoprotected environment that supports germ cell development. This ability has been extended to protection of SC and pancreatic islets when co-transplanted in both allo- and xenogeneic models. While SC are known to modulate immune responses, the mechanisms behind their control of the microenvironment are not fully elucidated. We hypothesized that SC express complement system inhibitors and anti-inflammatory markers, allowing them to survive complement-mediated death. Neonatal porcine SC were isolated, frozen at -80 °C, thawed, and analyzed for growth and viability. SC showed increased growth and restored viability up to day 7 post- thaw. SC were incubated with Normal Human Serum (NHS; containing antibodies and active complement) for 1.5 hours, while control groups were kept in DMEM. Porcine aortic endothelial cells (PAEC) were used as a killing control. SC survived this exposure to NHS on days 1, 3, 5, and 7, while PAEC had decreased survival. Gene expression analysis revealed upregulation of Ccl2 on day 1, and Tnfaip3 and Ccl20 on all days (NF-κB pathway downregulation/T regulatory cell activation), and no changes in Comp and Ptx3 (membrane disruption/cell death) after NHS exposure. These results suggest that SC can evade immune responses by expressing anti-inflammatory chemokines, making them a promising candidate for transplantation due to their ability to survive complement attack and promote a tolerogenic microenvironment. Topic Categories Transplantation Immunology (TRAN)