Immune checkpoints and reproductive immunology: Pioneers in the future therapy of infertility related Disorders?

As co-stimulatory receptors, immune checkpoint molecules are found on the surface of various immune cells and transduce inhibitory signals following ligand binding. The most studied members in this regard include PD-1, TIM-3, and CTLA-4. The physiological part immune checkpoints possess is the prevention of dangerous immune attacks towards self-antigens throughout an immune response, which takes place through the negative regulation of the effector immune cells, through the induction of T-cell exhaustion, for instance. It has recently been suggested that each checkpoint reduces immunoactivation via distinct intracellular mechanisms of signaling. Regulators of immune checkpoints are supposed to participate actively in immune defense mechanisms against infections, preventing autoimmunity, transplantation, and tumor immune evasion. In pregnancy, as an active immunotolerance mechanism which is also natural, the maternal immune system encounters two simultaneous challenges; in addition to accepting the semi-allogeneic fetus, the maternal immune system should also prevent infections. In this regard, the part immune checkpoint molecules possess is particularly interesting. Herein, the current understanding of such part in reproductive immunology is described.