Immunoprotective Properties of Primary Sertoli Cells in Mice: Potential Functional Pathways that Confer Immune Privilege1

Abstract

Primary Sertoli cells isolated from mouse testes survive when transplanted across immunological barriers and protect cotransplanted allogeneic and xenogeneic cells from rejection in rodent models. In contrast, the mouse Sertoli cell line (MSC-1) lacks immunoprotective properties associated with primary Sertoli cells. In this study, enriched primary Sertoli cells or MSC-1 cells were transplanted as allografts into the renal subcapsular area of naive BALB/c mice, and their survival in graft sites was compared. While Sertoli cells were detected within the grafts with 100% graft survival throughout the 20-day study, MSC-1 cells were rejected between 11 and 14 days, with 0% graft survival at 20 days posttransplantation. Nonetheless, the mechanism for primary Sertoli cell survival and immunoprotection remains unresolved. To identify immune factors or functional pathways potentially responsible for immune privilege, gene expression profiles of enriched primary Sertoli cells were compared with those of MSC-1 cells. Microarray analysis identified 2369 genes in enriched primary Sertoli cells that were differentially expressed at ±4-fold or higher levels than in MSC-1 cells. Ontological analyses identified multiple immune pathways, which were used to generate a list of 340 immune-related genes. Three functions were identified in primary Sertoli cells as potentially important for establishing immune privilege: suppression of inflammation by specific cytokines and prostanoid molecules, slowing of leukocyte migration by controlled cell junctions and actin polymerization, and inhibition of complement activation and membrane-associated cell lysis. These results increase our understanding of testicular immune privilege and, in the long-term, could lead to improvements in transplantation success.

Reduced Immunogenicity of Induced Pluripotent Stem Cells Derived from Sertoli Cells

“…Cells expressed the Sertoli cell marker Gata4 [17] and were negative for Dazl1 [24] and Vasa [25] (germ cells), Oct4 and Nanog (spermatogonial stem cells, [26]) and Hsd3β6 (Leydig cells, [27]) (Figure S1B). …”

Sertoli cells – Immunological sentinels of spermatogenesis

“…These are just few examples of immunoregulatory factors expressed by SCs. From our microarray analyses data we know that SCs are capable of producing a wide variety of immunoregulatory factors, which could be impacting the immune system [73]. Nonetheless, their exact role in inducing tolerogenic immune cells needs further investigation.…”

“…3b). Recently, through microarray analyses and qRT-PCR we have demonstrated for the first time that SCs express serine protease inhibitor (SERPIN)G1 [73]. SERPING1 targets the initial step of complement cascade activation i.e.…”

“…C1 complex thereby preventing the formation of C3 convertase (Fig. 3b) [73]. SCs also express or secrete apoptosis inhibitors such as serpina3n and protease inhibitor-9, which can inhibit NK and T cell-mediated death (Fig.…”

Renoprotective Effects of Cotransplanted Allogeneic Testicular Sertoli Cells in a Renal Acute Rejection Model in Rats

“…[4][5][6][7][8][9][10][11][12][13] In cotransplanted with allogeneic cells, Sertoli cells not only are immune privileged, but also assist fibromyoblasts and islet cells in escaping immune rejection, which allows the long-term survival of the grafts. [14][15][16][17][18][19] Such privilege is thought to be associated with the FasL expressed on the surface of Sertoli cells.…”