Extracellular Nucleotides on Lymphocyte Function

Nucleotides are basic components of cellular nucleic acids and therefore are a fundamental part of the organism. In several circumstances, however, nucleotides can be released into the extracellular environment through varied mechanisms. Once in the extracellular milieu, nucleotides can bind to and signal through surface receptors, which are called purinergic receptors. These signals typically vary depending on the ligand-receptor interaction; in general, extracellular ATP (eATP) leads to cell activation while adenosine mediates inhibitory signals. This is especially well-defined in immune cells, where the balance between the presence of eATP and adenosine receptors dictate the functional state of certain immune cell subsets and how efficiently the immune system fights tumors, for example. In lymphocytes (comprised by T and B cells, and innate lymphocytes), a sharp increase in research efforts helped us to understand some of the complexity of the downstream consequences of nucleotide signaling. Yet, much of how extracellular nucleotides operate in distinct lymphocyte subsets is still unknown. Among many unanswered questions, some are highlighted below:

- How ADP and AMP-binding purinergic receptors influence canonical T and B cell responses?
- What are the relevant sources of extracellular nucleotides in healthy versus infected/inflamed organs?
- Can purinergic signaling help us understand more about the function and homeostasis of innate lymphocytes?

In this Research Topic, we encourage researchers from across the globe to submit Review and Original Research articles to shed light on this important and novel area of immunology and cell physiology.