Tissue-and temporal-specific roles of extracellular ATP on T cell metabolism and function

The activation and function of T cells is fundamental for the control of infectious diseases and cancer, and conversely can mediate several autoimmune diseases. Among the signaling pathways leading to T cell activation and function, the sensing of extracellular adenosine triphosphate (eATP) has been recently appreciated as an important component. Through a plethora of purinergic receptors, most prominently P2RX7, eATP sensing can induce a wide variety of processes in T cells, such as proliferation, subset differentiation, survival, or cell death. The downstream roles of eATP sensing can vary according to (a) the T cell subset, (b) the tissue where T cells are, and (c) the time after antigen exposure. In this mini-review, we revisit the recent findings on how eATP signaling pathways regulate T-cell immune responses and posit important unanswered questions on this field.