Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells

Kaur, Gurvinder; Wright, Kandis; Mital, Payal; Hibler, Taylor; Miranda, Jonathan M; Thompson, Lea Ann; Halley, Katelyn; Dufour, Jannette M.

doi:10.1177/0963689720947102

Cited by 19 publications

(32 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, they act as immunological sentinels of spermatogenesis by not only forming the blood-testis barrier, but also expressing immunoregulatory factors [2]. Sertoli cell/islet cograft shows that the infusion of SCs into islet transplantation effectively prolonged the survival of islet grafts by reducing CD4 + and CD8 + T cells but increasing the CD4 + or CD8 + Tregs [109,110]. Interestingly, while syngeneic SCs help to impede CD8 + T cell infiltration through the formation of a tubule structure, allogeneic SCs fail to form this structure and prevent the infiltration of active immune cells, thus having a detrimental effect on islet graft survival [111].…”

Section: T Lymphocytes and Sertoli Cellsmentioning

confidence: 99%

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes

Gong

Zeng

et al. 2020

IJMS

View full text Add to dashboard Cite

The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility. Different T cell subsets have been identified in mammalian testes, which may be involved in the maintenance of immune tolerance and pathogenic immune responses in testicular infection and inflammation. We reviewed the evidence in the published literature on different T subtypes (regulatory T cells, helper T cells, cytotoxic T cells, γδ T cells, and natural killer T cells) in human and animal testes that support their regulatory roles in infertility and the orchitis pathology. While many in vitro studies have indicated the regulation potential of functional T cell subsets and their possible interaction with Sertoli cells, Leydig cells, and spermatogenesis, both under physiological and pathological processes, there have been no in situ studies to date. Nevertheless, the normal distribution and function of T cell subsets are essential for the immune privilege of the testes and intact spermatogenesis, and T cell-mediated immune response drives testicular inflammation. The distinct function of different T cell subsets in testicular homeostasis and the orchitis pathology suggests a considerable potential of targeting specific T cell subsets for therapies targeting chronic orchitis and immune infertility.

show abstract

Section: T Lymphocytes and Sertoli Cellsmentioning

confidence: 99%

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes

Gong

Zeng

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…However, rejecting Sertoli cell/islet co-grafts showed increased numbers of macrophages and T cells ( 96 ). These results are mirrored in xenotransplantation experiments, in which ectopically grafted neonatal pig Sertoli cells were able to reduce the overall number of macrophages and CD3 T cells, and increase the number of Tregs ( 43 ).…”

Section: Sertoli Cell Protective Response In the Testis And Summary O...mentioning

confidence: 75%

“…Similar results were observed in vivo where neonatal pig Sertoli cells after transplantation under the kidney capsule of nonimmune suppressed rats inhibited complement activation, specifically C3 deposition and MAC formation ( 36 ). At the same time there was reduced migration of APCs and increased Treg migration that may be at least partly due to the presence of fewer anaphylatoxins (C3a and C5a) ( 43 ). CD59, CD46, CD55, and CD59 also play important roles in sperm development, transit through male and female reproductive tracts, and fertility ( 44 ).…”

Section: Sertoli Cell Protective Response In the Testis And Summary O...mentioning

confidence: 99%

Sertoli Cell Immune Regulation: A Double-Edged Sword

et al. 2022

View full text Add to dashboard Cite

The testis must create and maintain an immune privileged environment to protect maturing germ cells from autoimmune destruction. The establishment of this protective environment is due, at least in part, to Sertoli cells. Sertoli cells line the seminiferous tubules and form the blood-testis barrier (BTB), a barrier between advanced germ cells and the immune system. The BTB compartmentalizes the germ cells and facilitates the appropriate microenvironment necessary for spermatogenesis. Further, Sertoli cells modulate innate and adaptive immune processes through production of immunoregulatory compounds. Sertoli cells, when transplanted ectopically (outside the testis), can also protect transplanted tissue from the recipient’s immune system and reduce immune complications in autoimmune diseases primarily by immune regulation. These properties make Sertoli cells an attractive candidate for inflammatory disease treatments and cell-based therapies. Conversely, the same properties that protect the germ cells also allow the testis to act as a reservoir site for infections. Interestingly, Sertoli cells also have the ability to mount an antimicrobial response, if necessary, as in the case of infections. This review aims to explore how Sertoli cells act as a double-edged sword to both protect germ cells from an autoimmune response and activate innate and adaptive immune responses to fight off infections.

show abstract

“…Therefore, the physical sequestration of these antigens is a critical function of Sertoli cells and suggests that Sertoli polarization, including proper basal localization of the BTB, is vital for spermatogenesis . Beyond establishing the BTB, Sertoli cells also modulate the immune environment in general via the secretion of cytokines and other factors, as it has been shown that Sertoli cells can significantly enhance the success of xenotransplantation in other organs (Doyle et al, 2012;Dufour et al, 2003;Kaur et al, 2014Kaur et al, , 2020.…”

Section: Introductionmentioning

confidence: 99%

Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis

et al. 2021

View full text Add to dashboard Cite

Sertoli cells are highly polarized testicular supporting cells that simultaneously nurture multiple stages of germ cells during spermatogenesis. Proper localization of polarity protein complexes within Sertoli cells, including those responsible for blood-testis barrier formation, is vital for spermatogenesis. However, the mechanisms and developmental timing that underlie Sertoli cell polarity are poorly understood. We investigate this aspect of testicular function by conditionally deleting Cdc42, encoding a Rho GTPase involved in regulating cell polarity, specifically in Sertoli cells. Sertoli Cdc42 deletion leads to increased apoptosis and disrupted polarity of juvenile and adult testes but does not affect fetal and postnatal testicular development. The onset of the first wave of spermatogenesis occurs normally, but it fails to progress past round spermatid stages, and by young adulthood, conditional knockout males exhibit a complete loss of spermatogenic cells. These findings demonstrate that Cdc42 is essential for Sertoli cell polarity and for maintaining steady-state sperm production.

show abstract

Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells

Cited by 19 publications

References 68 publications

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes

Sertoli Cell Immune Regulation: A Double-Edged Sword

Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis

Contact Info

Product

Resources

About