Testicular immune privilege revisited: when protection fails.

Infertility impacts roughly 1 in 6 adults globally, where 50% of infertility cases are because of male factors. It is estimated that up to 15% of male infertility cases are because of disruption of testicular immune regulation. Thus, understanding mechanisms of immune privilege dysregulation resulting in blood-testis barrier disruption and germ cell loss could bring us one step closer to identifying ways to address infertility issues. In this views and reviews article, we introduce how testicular immune privilege is established at the blood-testis barrier through junction proteins between adjacent Sertoli cells and surrounding testicular and immune cells, and discuss how immune protection fails because of infections, cancers, and traumas. Finally, we discuss clinical considerations when immune privilege has failed, including attention for clinical counseling, infertility workups, and fertility preservation approaches.