Channel plan: control of adaptive immune responses by pannexins.

Pannexins (PANXs) are expressed by mammalian immune and nonimmune cells and promote the export of many <1-kDa small molecules, at steady-state or in response to disease. In mice and humans, PANX1 is a crucial regulator of lung adaptive immunity, controlling conventional and regulatory CD4+ T cell immune responses to lung allergens. PANX1 supports the development of mouse CD8+ T cell effector and memory responses, via the export of extracellular ATP and induction of lactate recycling to induce full CD8+ T cell activation. PANX3 on murine bone marrow (BM) osteoblasts maintains BM plasma cells by its ATP-releasing function. Pannexin (PANX) channels mediate the release of small molecules (e.g., ATP) and play a fundamental role in the export of metabolites in healthy or disease contexts. Recent advances define some of the roles of PANXs in T and B cell responses in vivo and highlight the importance of these channels in the regulation of adaptive immune responses. The development of mammalian adaptive (i.e., B and T cell-mediated) immune responses is tightly controlled at transcriptional, epigenetic, and metabolic levels. Signals derived from the extracellular milieu are crucial regulators of adaptive immunity. Beyond the traditionally studied cytokines and chemokines, many other extracellular metabolites can bind to specialized receptors and regulate T and B cell immune responses. These molecules often accumulate extracellularly through active export by plasma membrane transporters. For example, mammalian immune and non-immune cells express pannexin (PANX)1–3 channels on the plasma membrane, which release many distinct small molecules, notably intracellular ATP. Here, we review novel findings defining PANXs as crucial regulators of T and B cell immune responses in disease contexts such as cancer or viral infections. [ABSTRACT FROM AUTHOR]