Expression of Hv1 proton channels in myeloid-derived suppressor cells (MDSC) and its potential role in T cell regulation

被引：12

作者：

Alvear-Arias, Juan J. ^{[1
,2
]}

Carrillo, Christian ^{[1
,2
]}

Paz Villar, Javiera ^{[1
]}

Garcia-Betancourt, Richard ^{[1
,7
]}

Pena-Pichicoi, Antonio ^{[1
,2
]}

Fernandez, Audry ^{[1
]}

Fernandez, Miguel ^{[1
,2
]}

Carmona, Emerson M. ^{[1
,8
]}

Pupo, Amaury ^{[1
]}

Neely, Alan ^{[1
]}

Alvarez, Osvaldo ^{[1
,3
]}

Garate, Jose ^{[1
,2
]}

Barajas-Martinez, Hector ^{[4
]}

Peter Larsson, H. ^{[5
]}

Lopez-Rodriguez, Angelica ^{[6
]}

Latorre, Ramon ^{[1
]}

Gonzalez, Carlos ^{[1
,2
,3
]}

机构：

[1] Univ Valparaiso, Fac Ciencias, Millenium Inst Ctr Interdisciplinario Neurocienci, Valparaiso 2360102, Chile

[2] Univ Valparaiso, Millenium Nucleus NanoBioPhys NNBP, Valparaiso 2360102, Chile

[3] Univ Chile, Fac Ciencias, Dept Biol, Santiago 7800003, Chile

[4] Lankenau Inst Med Res, Cardiovasc Res, Wynnewood, PA 19096 USA

[5] Univ Miami, Dept Physiol & Biophys, Coral Gables, FL 33101 USA

[6] Univ Juarez Estado Durango, Fac Ciencias Quim, Durango 34000, Mexico

[7] Univ Chile, Fac Med, Inst Ciencias Biomed, Millennium Inst Immunol & Immunotherapy,Programa, Santiago 8380453, Chile

[8] Texas Tech Univ, Cell Physiol & Mol Biophys, Hlth Sci Ctr, Lubbock, TX 79430 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2022年 / 119卷 / 15期

基金：

芬兰科学院;

关键词：

myeloid cells; H(v)1 channel; immunosuppression; NOX2; complex; ROS; NADPH OXIDASE; IMMUNE SUPPRESSION; HV1; MECHANISM; ANTIGEN; CANCER; INHIBITION; CURRENTS; PH; MICROENVIRONMENT;

D O I：

10.1073/pnas.2104453119

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 H(v)1 proton channel in certain immune cells to support sustained free-radical production. However, a functional expression of the H(v)1 channel in MDSC has not yet been reported. Here, we demonstrate that mouse MDSC express functional H(v)1 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 H(v)1 a potential drug target for cancer treatment.

引用

页数：10

共 62 条

[1] The inhibition of voltage-gated H+ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis [J].