Aquaporin 4 inhibition alters chemokine receptor expression and T cell trafficking

Michael Nicosia, Satoshi Miyairi, Ashley Beavers, George W. Farr, Paul R. McGuirk, Marc F. Pelletier, Anna Valujskikh

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Aquaporins (AQPs) are water channels that mediate a variety of biological processes. However, their role in the immune system is poorly understood. We recently reported that AQP4 is expressed by naïve and memory T cells and that AQP4 blockade with a small molecule inhibitor prolongs murine heart allograft survival at least partially through diminishing T cell activation, proliferation and trafficking. The goal of this study was to determine how AQP4 function impacts T cells in the absence of antigen stimulation. AQP4 inhibition transiently reduced the number of circulating CD4+ and CD8+ T cells in naïve non-transplanted mice in the absence of systemic T cell depletion. Adoptive transfer studies demonstrated T cell intrinsic effect of AQP4 inhibition. AQP4 blockade altered T cell gene and protein expression of chemokine receptors S1PR1 and CCR7, and their master regulator KLF-2, and reduced chemotaxis toward S1P and CCL21. Consistent with the in vitro data, in vivo AQP4 inhibition reduced T lymphocyte numbers in the lymph nodes with simultaneous accumulation in the liver. Our findings indicate that blocking AQP4 reversibly alters T lymphocyte trafficking pattern. This information can be explored for the treatment of undesirable immune responses in transplant recipients or in patients with autoimmune diseases.

Original languageEnglish (US)
Article number7417
JournalScientific reports
Issue number1
StatePublished - Dec 1 2019
Externally publishedYes

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© 2019, The Author(s).


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