TY  - JOUR
AU  - Coe, David
AU  - Poobalasingam, Thanushiyan
AU  - Fu, Hongmei
AU  - Bonacina, Fabrizia
AU  - Wang, Guosu
AU  - Morales, Valle
AU  - Moregola, Annalisa
AU  - Mitro, Nico
AU  - Cheung, Kenneth Cp
AU  - Ward, Eleanor J
AU  - Nadkarni, Suchita
AU  - Aksentijevic, Dunja
AU  - Bianchi, Katiuscia
AU  - Norata, Giuseppe Danilo
AU  - Capasso, Melania
AU  - Federica, Marelli-Berg
TI  - Loss of voltage-gated hydrogen channel 1 expression reveals heterogeneous metabolic adaptation to intracellular acidification by T cells.
JO  - JCI insight
VL  - 7
IS  - 10
SN  - 2379-3708
CY  - Ann Arbor, Michigan
PB  - JCI Insight
M1  - DZNE-2022-01114
SP  - e147814
PY  - 2022
N1  - (CC BY 4.0)
AB  - Voltage-gated hydrogen channel 1 (Hvcn1) is a voltage-gated proton channel, which reduces cytosol acidification and facilitates the production of ROS. The increased expression of this channel in some cancers has led to proposing Hvcn1 antagonists as potential therapeutics. While its role in most leukocytes has been studied in depth, the function of Hvcn1 in T cells remains poorly defined. We show that Hvcn1 plays a nonredundant role in protecting naive T cells from intracellular acidification during priming. Despite sharing overall functional impairment in vivo and in vitro, Hvcn1-deficient CD4+ and CD8+ T cells display profound differences during the transition from naive to primed T cells, including in the preservation of T cell receptor (TCR) signaling, cellular division, and death. These selective features result, at least in part, from a substantially different metabolic response to intracellular acidification associated with priming. While Hvcn1-deficient naive CD4+ T cells reprogram to rescue the glycolytic pathway, naive CD8+ T cells, which express high levels of this channel in the mitochondria, respond by metabolically compensating mitochondrial dysfunction, at least in part via AMPK activation. These observations imply heterogeneity between adaptation of naive CD4+ and CD8+ T cells to intracellular acidification during activation.
KW  - Hydrogen
KW  - Hydrogen-Ion Concentration
KW  - Lymphocyte Count
KW  - Protons
KW  - Signal Transduction
KW  - Adaptive immunity (Other)
KW  - Immunology (Other)
KW  - Protons (NLM Chemicals)
KW  - Hydrogen (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9220931
C6  - pmid:35472029
DO  - DOI:10.1172/jci.insight.147814
UR  - https://pub.dzne.de/record/164565
ER  -