Sertoli cells – Immunological sentinels of spermatogenesis

Abstract

Testicular germ cells, which appear after the establishment of central tolerance, express novel cell surface and intracellular proteins that can be recognized as ‘foreign antigens’ by the host’s immune system. However, normally these germ cells do not evoke an auto-reactive immune response. The focus of this manuscript is to review the evidence that the Blood-Testis-Barrier (BTB)/Sertoli cell (SC) barrier along with the SCs ability to modulate the immune response is vital for protecting auto-antigenic germ cells. In normal testis, the BTB/SC barrier protects the majority of the auto-antigenic germ cells by limiting access by the immune system and sequestering these ‘new antigens’. SCs also modulate testis immune cells (induce regulatory immune cells) by expressing several immunoregulatory factors, thereby creating a local tolerogenic environment optimal for survival of nonsequesetred auto-antigenic germ cells. Collectively, the fortress created by the BTB/SC barrier along with modulation of the immune response is pivotal for completion of spermatogenesis and species survival.

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

“…The immuneprivileged feature of the testis was first discovered in 1767, when John Hunter transplanted rooster testes into the abdominal cavity of a hen, and he found that they maintained their normal structure over time [76]. Several studies have demonstrated that SeC are the most relevant cell type of the testis that can protect testicular allogeneic and xenogeneic grafts from immune rejection, even if transplanted outside the BTB, thus confirming that humoral besides mechanic processes are involved in the immuneprivileged status of the testes [75,77,78]. Evidence that SeC are primarily responsible for the successful survival and function of transplanted tissues was provided when SeC were co-transplanted with allogeneic Langerhans islets, showing that SeC were able to protect islets from rejection in the absence of immunosuppression [79].…”

“…One of the most recent approaches is centered on the peculiarities of SeC, which have a physiological role in protecting the developing germ cells through the production of immunomodulatory factors, and in favoring germ cell maturation thanks to the secretion of trophic factors [75,78]. Purified SPF porcine SeC were encapsulated and injected into the peritoneal cavity of mdx mice.…”

A somatic permeability barrier around the germline is essential for Drosophila spermatogenesis

“…The soma-germline barrier has been proposed to play diverse roles in the testis, but chief among them is its proposed function in regulating the germline signaling environment during differentiation França et al, 2012;Lui et al, 2003b). Additionally, it is thought that the soma-germline barrier protects the germline from cytotoxic materials (Su et al, 2011) and from the immune system in vertebrates (Kaur et al, 2014).…”

A new threat on the horizon — Zika virus and male fertility

“…Immune privilege in the testis is mandatory when neoantigens appear on the meiotic and postmeiotic germ cells at puberty, long after the establishment of self-tolerance around birth. In immune privilege, the function of Sertoli cells extends beyond effectively restricting the access of leukocytes to the developing germ cells by the blood-testis barrier; this is illustrated by studies showing that pancreatic islets survive much longer when cotransplanted with Sertoli cells 4,5 . These data clearly indicate that the role of Sertoli cells in preserving immune privilege goes way beyond a simple barrier function and probably relies on secreted and surface immunosuppressive or immunoregulatory factors 4 .…”

“…In immune privilege, the function of Sertoli cells extends beyond effectively restricting the access of leukocytes to the developing germ cells by the blood-testis barrier; this is illustrated by studies showing that pancreatic islets survive much longer when cotransplanted with Sertoli cells 4,5 . These data clearly indicate that the role of Sertoli cells in preserving immune privilege goes way beyond a simple barrier function and probably relies on secreted and surface immunosuppressive or immunoregulatory factors 4 . In the case of an infection, this function could prove to be a double-edged sword: what was previously beneficial in protecting the sensitive germ cells by the provision of a tightly controlled anti-inflammatory immune environment under normal conditions can render these cells particularly prone to infection by microbes.…”