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. 2021 Dec 13;12:793924. doi: 10.3389/fphys.2021.793924

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Copyright © 2021 Ertuglu, Elijovich, Laffer and Kirabo.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Activation of ENaC in antigen presenting cells (APC) leading to isoleuvoglandin (IsoLG) formation and activation of CD8⁺ T cells. Elevated interstitial sodium (Na⁺) enters APCs, in particular dendritic cells, through ENaC and triggers intracellular calcium entry via the sodium calcium exchanger. The increased intracellular calcium activates protein kinase C (PKC), which in turn activates NAPDH oxidase via phosphorylation of p47phox. Superoxide and ROS formation by NAPDH oxidase leads to IsoLG production, which adduct to the lysine residues in proteins and form IsoLG adducts that are presented as neoantigens and trigger CD8⁺ T cells activation. The figure created with BioRender.com.