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

Author:

Nicosia Michael1ORCID,Lee Juyeun2ORCID,Beavers Ashley1,Kish Danielle1,Farr George W3,McGuirk Paul R3,Pelletier Marc F3,Lathia Justin D2,Fairchild Robert L1,Valujskikh Anna1

Affiliation:

1. Department of Inflammation and Immunity, Lerner Research Institute , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 , United States

2. Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 , United States

3. Aeromics Inc., 470 James Street Suite 007 , New Haven, CT 06513 , United States

Abstract

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 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.

Funder

NIH

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Immunology,Immunology and Allergy

Reference51 articles.

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