論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC04364 |