| RRC ID |
55783
|
| 著者 |
Nicosia M, Miyairi S, Beavers A, Farr GW, McGuirk PR, Pelletier MF, Valujskikh A.
|
| タイトル |
Aquaporin 4 inhibition alters chemokine receptor expression and T cell trafficking.
|
| ジャーナル |
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.
|
| 巻・号 |
9(1)
|
| ページ |
7417
|
| 公開日 |
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
|
| 引用数 |
1
|
| リソース情報 |
| 実験動物マウス |
RBRC04364 |
