Modulation of regulatory T cell function and stability by co-inhibitory receptors

Co-inhibitory receptor signalling - through CTLA4, LAG3, PD1, TIGIT, NRP1 and TIM3 - controls the function and stability of regulatory T cells in autoimmunity and cancer and could therefore be amenable to therapeutic targeting. Regulatory T (T-reg) cells constitute a dynamic population that is essential for controlling immune responses in health and disease. Defects in T(reg)cell function and decreases in T(reg)cell numbers have been observed in patients with autoimmunity and the opposite effects on T(reg)cells occur in cancer settings. Current research on new therapies for these diseases is focused on modulating T(reg)cell function to increase or decrease suppressive activity in autoimmunity and cancer, respectively. In this regard, several co-inhibitory receptors that are preferentially expressed by T(reg)cells under homeostatic conditions have recently been shown to control T(reg)cell function and stability in different disease settings. These receptors could be amenable to therapeutic targeting aimed at modulating T(reg)cell function and plasticity. This Review summarizes recent data regarding the role of co-inhibitory molecules in the control of T(reg)cell function and stability, with a focus on their roles and potential therapeutic use in autoimmunity and cancer.