Expression of H v 1 proton channels in myeloid-derived suppressor cells (MDSC) and its potential role in T cell regulation

• Published in: Proceedings of the National Academy of Sciences - PNAS 2022-04, Vol.119 (15), p.e2104453119
• Main Authors: Alvear-Arias, Juan J, Carrillo, Christian, Villar, Javiera Paz, Garcia-Betancourt, Richard, Peña-Pichicoi, Antonio, Fernandez, Audry, Fernandez, Miguel, Carmona, Emerson M, Pupo, Amaury, Neely, Alan, Alvarez, Osvaldo, Garate, Jose, Barajas-Martinez, Héctor, Larsson, H Peter, Lopez-Rodriguez, Angélica, Latorre, Ramon, Gonzalez, Carlos
• Format: Article
• Language: English
• Subjects: Animals; Ion Channels - genetics; Ion Channels - metabolism; Mice; Myeloid-Derived Suppressor Cells - immunology; NADPH Oxidase 2 - metabolism; Protons; Reactive Oxygen Species - metabolism; T-Lymphocytes - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2104453119

Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population with high immunosuppressive activity that proliferates in infections, inflammation, and tumor microenvironments. In tumors, MDSC exert immunosuppression mainly by producing reactive oxygen species (ROS), a process triggered by the NADPH oxidase 2 (NOX2) activity. NOX2 is functionally coupled with the Hv1 proton channel in certain immune cells to support sustained free-radical production. However, a functional expression of the Hv1 channel in MDSC has not yet been reported. Here, we demonstrate that mouse MDSC express functional Hv1 proton channel by immunofluorescence microscopy, flow cytometry, and Western blot, besides performing a biophysical characterization of its macroscopic currents via patch-clamp technique. Our results show that the immunosuppression by MDSC is conditional to their ability to decrease the proton concentration elevated by the NOX2 activity, rendering Hv1 a potential drug target for cancer treatment.