About this Research Topic
Interestingly much less is known about nicotinamide adenine dinucleotide (NAD), another highly abundant intracellular molecule used as energy currency. Intracellularly, NAD and its metabolic products ADP-ribose (ADPR), 2’-deoxy-ADPR (from 2’deoxy-NAD), cyclic ADPR (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are important second messengers essential for leukocyte Ca2+ signaling. Metabolism of these signaling molecules, as well as their exact molecular targets, are still unknown in many aspects, despite their importance for central processes of adaptive immunity, e.g. T cell activation. Further, there are only a few cell surface receptors identified, such as P2Y1 and P2Y11 that can sense extracellular NAD. Of note, the extracellular signaling capacity of NAD is broadened by various nucleotide-degrading cell surface (ecto-) enzymes that can generate a variety of other nucleotide metabolites: ecto-CD38 metabolizes NAD into ADPR and cADPR, ecto-nucleotide pyrophosphatases (ENPPs) such as ENPP1 generate adenosine monophosphate (AMP) directly from NAD or from ADPR, thereby providing substrate for CD73-catalyzed adenosine generation and ligands for P1 receptors. Ecto-ADP-ribosyltransferases (ARTCs) utilize extracellular NAD to covalently attach ADPR groups to arginine residues of multiple different cell surface proteins, including P2X7, resulting in a post-translational modification that can significantly affect the function of the modified target. In summary, NAD and its metabolites inside and outside of cells can have a remarkable impact on many different regulatory pathways of immunity.
The goal of this Research Topic is to collect high-quality Review and Original Research articles that focus on the role and function of intracellular and extracellular NAD and NAD-derived metabolites as modulators of immunity. We welcome submissions that cover the following topics:
- Receptors on immune cells that can sense extracellular NAD.
- Intracellular signaling by NAD derivatives/metabolic products in immune cells
- NAD-utilizing ecto-enzymes and the impact of their catalytic products on immune cell functions
- Mechanisms of NAD release during an immune response
- Pharmacological manipulation of receptors/enzymes involved in NAD signaling in immunity
Keywords: nicotinamide adenin dinucleotide, NAD, cADPR, purinergic signalling, ecto-nucleotidases
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