The Sertoli cell: one hundred fifty years of beauty and plasticity.

It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.

Therapeutic potential of immune privileged Sertoli cells

Sertoli Cells (SCs) in the testes have evolved to possess unique immune privileged properties to protect the developing germ cells from immunological attack. These immune privileged properties are not restricted to the testis, as SCs survive when transplanted across immunological barriers as allo- and xeno-grafts. Here we discuss the therapeutic potential of transplanted SCs in protecting cells, tissues or organs, which could be paramount in the field of transplantation to treat life-threatening diseases. Similar to the testis, transplanted SCs inhibit and/or modulate the immune response locally (at the transplant site) or systemically. Protection of transplanted cells, present in close vicinity of SCs, along with reduction of inflammation at the transplant site support that SC can inhibit and/or modulate the immune response locally. While protection of skin, islets in the contralateral kidney, and organs by SCs support their role in inducing systemic tolerance. Additionally, amelioration of autoimmune diseases, specifically type 1 diabetes mellitus, further supports this notion. Studies exploring SCs role as a vehicle for the cell based gene therapy further widens the horizon of SCs therapeutic potential in transplantation.

Therapeutic potential of immune privileged Sertoli cells

Sertoli Cells (SCs) in the testes have evolved to possess unique immune privileged properties to protect the developing germ cells from immunological attack. These immune privileged properties are not restricted to the testis, as SCs survive when transplanted across immunological barriers as allo- and xeno-grafts. Here we discuss the therapeutic potential of transplanted SCs in protecting cells, tissues or organs, which could be paramount in the field of transplantation to treat life-threatening diseases. Similar to the testis, transplanted SCs inhibit and/or modulate the immune response locally (at the transplant site) or systemically. Protection of transplanted cells, present in close vicinity of SCs, along with reduction of inflammation at the transplant site support that SC can inhibit and/or modulate the immune response locally. While protection of skin, islets in the contralateral kidney, and organs by SCs support their role in inducing systemic tolerance. Additionally, amelioration of autoimmune diseases, specifically type 1 diabetes mellitus, further supports this notion. Studies exploring SCs role as a vehicle for the cell based gene therapy further widens the horizon of SCs therapeutic potential in transplantation.(AU)

Testisimmune privilege - Assumptions versus facts.

The testis has long enjoyed a reputation as an immunologically privileged site based on its ability to protect auto-antigenic germ cells and provide an optimal environment for the extended survival of transplanted allo- or xeno-grafts. Exploration of the role of anatomical, physiological, immunological and cellular components in testis immune privilege revealed that the tolerogenic environment of the testis is a result of the immunomodulatory factors expressed or secreted by testicular cells (mainly Sertoli cells, peritubular myoid cells, Leydig cells, and resident macrophages). The blood-testis barrier/Sertoli cell barrier, is also important to seclude advanced germ cells but its requirement in testis immune privilege needs further investigation. Testicular immune privilege is not permanent, as an effective immune response can be mounted against transplanted tissue, and bacterial/viral infections in the testis can be effectively eliminated. Overall, the cellular components control the fate of the immune response and can shift the response from immunodestructive to immunoprotective, resulting in immune privilege.

Testis immune privilege - Assumptions versus facts

The testis has long enjoyed a reputation as a n immunologically privileged site based on its ability to protect auto - antigenic germ cells and provide an optimal environment for the extended survival of transplanted allo - or xeno - grafts. Exploration of the role of anatomical, physiological, immunologica l and cell ular components in testis immune privilege reveal ed that the tolerogenic environment of the test i s is a result of the immunomodulatory factors expressed or secreted by testicular cells (mainly Sertoli cells, peritubular myoid cells, Leydig cells , and resident macrophages ). The b lood - testis barrier/Sertoli cell barrier, is also important to seclude advanced germ cells but its requirement in testis immune privilege needs further investigation . T esticular immune privilege is not permanent , as an effe ctive immune response can be mounted against transplanted tissue , and bacterial/viral infections in the testis can be effectively eliminated . Overall, the cellular components control the fate of the immune response and can shift the response from immunodestructive to immunoprotective, resulting in immuneprivilege.