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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Published in | Journal of leukocyte biology Vol. 113; no. 6; pp. 544 - 554 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
01.06.2023
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Subjects | |
Online Access | Get full text |
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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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Experiments were designed by MN, AV, JL, GF, MP, JDL, and RF. Experiments were carried out by MN, with assistance from AB and JL. Data were analyzed by MN. AQP4 inhibitors AER-270 and AER-271 were provided by GF, PM, and MP. The manuscript was written and prepared by MN and AV and edited by GF, MP, and RF. Author contributions |
ISSN: | 1938-3673 0741-5400 1938-3673 |
DOI: | 10.1093/jleuko/qiad010 |