RRC ID 55783
Author Nicosia M, Miyairi S, Beavers A, Farr GW, McGuirk PR, Pelletier MF, Valujskikh A.
Title Aquaporin 4 inhibition alters chemokine receptor expression and T cell trafficking.
Journal Sci Rep
Abstract 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.
Volume 9(1)
Pages 7417
Published 2019-5-15
DOI 10.1038/s41598-019-43884-2
PII 10.1038/s41598-019-43884-2
PMID 31092872
PMC PMC6520372
MeSH Animals Aquaporin 4 / antagonists & inhibitors* Aquaporin 4 / metabolism Chemotaxis Female Flow Cytometry Heart Transplantation Lymphocyte Activation Lymphocyte Count Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Osmotic Pressure Real-Time Polymerase Chain Reaction Receptors, CCR7 / metabolism* Sphingosine-1-Phosphate Receptors / metabolism* T-Lymphocytes / metabolism T-Lymphocytes / physiology*
IF 4.011
Times Cited 1
Mice RBRC04364