RRC ID 73664
Author Michael Nicosia, Juyeun Lee, Ashley Beavers, Danielle Kish, George W Farr, Paul R McGuirk, Marc F Pelletier, Justin D Lathia, Robert L Fairchild, Anna Valujskikh
Title Water channel Aquaporin 4 is required for T cell receptor mediated lymphocyte activation
Journal Journal of Leukocyte Biology
Abstract Aquaporins are a family of ubiquitously expressed transmembrane water channels implicated in a broad range of physiological functions. We have previously reported that Aquaporin 4 (AQP4) is expressed on T cells and that treatment with a small molecule AQP4 inhibitor significantly delays T cell mediated heart allograft rejection. Using either genetic deletion or small molecule inhibitor, we show that AQP4 supports T cell receptor mediated activation of both mouse and human T cells. Intact AQP4 is required for optimal T cell receptor (TCR) related signaling events, including nuclear translocation of transcription factors and phosphorylation of proximal TCR signaling molecules. AQP4 deficiency or inhibition impairs actin cytoskeleton rearrangements following TCR cross-linking, causing inferior TCR polarization and a loss of TCR signaling. Our findings reveal a novel function of AQP4 in T lymphocytes and identify AQP4 as a potential therapeutic target for preventing TCR-mediated T cell activation.
Published 2023-2-1
DOI 10.1093/jleuko/qiad010
PMID 36805947
IF 3.757
Mice RBRC04364