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

First Author  Nicosia M Year  2023
Journal  J Leukoc Biol Volume  113
Issue  6 Pages  544-554
PubMed ID  36805947 Mgi Jnum  J:336117
Mgi Id  MGI:7486287 Doi  10.1093/jleuko/qiad010
Citation  Nicosia M, et al. (2023) Water channel aquaporin 4 is required for T cell receptor mediated lymphocyte activation. J Leukoc Biol 113(6):544-554
abstractText  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.
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