Water channel aquaporin 4 is required for T cell receptor mediated lymphocyte activation

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 media...

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Bibliographic Details
Published in:Journal of leukocyte biology 2023-06, Vol.113 (6), p.544-554
Main Authors: Nicosia, Michael, Lee, Juyeun, Beavers, Ashley, Kish, Danielle, Farr, George W, McGuirk, Paul R, Pelletier, Marc F, Lathia, Justin D, Fairchild, Robert L, Valujskikh, Anna
Format: Article
Language:English
Subjects:
Animals
Aquaporin 4 - genetics
Aquaporin 4 - metabolism
Humans
Lymphocyte Activation
Mice
Receptors, Antigen, T-Cell
Signal Transduction
T-Lymphocytes
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Summary: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 crosslinking, 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.
ISSN:1938-3673
0741-5400
1938-3673
DOI:10.1093/jleuko/qiad010