Regulatory T cells (Tregs) are important for sperm tolerance and male fertility
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Regulatory T cells (Tregs) are specialized immune cells that modulate tissue homeostasis. They are a specialized subset of T lymphocytes that function as suppressive immune cells and inhibit various elements of immune response in vitro and in vivo. While there are constraints on the number or function of Tregs which can be exploited to evoke an effective anti-tumor response, sufficient expansion of Tregs is essential for successful organ transplantation and for promoting tolerance of self and foreign antigens. Current studies have provided evidence that a defect in the number or function of Tregs contributes to the etiology of several reproductive diseases.
In the male reproductive tract, prevention of autoimmune responses against antigenic spermatozoa, while ensuring protection against stressors, is a key determinant of fertility. Using an autoimmunity-induced model, it was uncovered that the role of Tregs in maintaining the tolerogenic state of the testis and epididymis. The loss of tolerance induced an exacerbated immune cell infiltration and the development of anti-sperm antibodies, which caused severe male subfertility. By identifying immunoregulatory mechanisms in the testis and epididymis.
Tregs modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing precision-targeting treatment strategies. Here, it was reported that Tregs maintain the tolerogenic state of the testis and epididymis, where sperm are produced and mature. It was found that Treg depletion induces severe autoimmune orchitis and epididymitis, manifested by an exacerbated immune cell infiltration [CD4 T cells, monocytes, and mononuclear phagocytes (MPs)] and the development of anti-sperm antibodies (ASA).
In Treg-depleted mice, MPs increased projections toward the epididymal lumen as well as invading the lumen. ASA-bound sperm enhance sperm agglutination and might facilitate sperm phagocytosis. Tolerance breakdown impaired epididymal epithelial function and altered extracellular vesicle cargo, both of which play crucial roles in the acquisition of sperm fertilizing ability and subsequent embryo development. The affected mice had reduced sperm number and motility and severe fertility defects.
Deciphering these immunoregulatory mechanisms may lead to the development of therapies for infertility and identifying potential targets for immuno-contraception. Ultimately, such knowledge fills gaps related to reproductive mucosa, which is an understudied facet of human male health.
References:
https://www.pnas.org/doi/10.1073/pnas.2306797120
https://pubmed.ncbi.nlm.nih.gov/24048122/
https://pubmed.ncbi.nlm.nih.gov/34845322/
https://pubmed.ncbi.nlm.nih.gov/34845322/