Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension
Objective—Survival of immune and nonimmune cells relies on Axl, a receptor tyrosine kinase, which is implicated in hypertension. Activated T lymphocytes are involved in regulation of high blood pressure. The goal of the study was to investigate the role of Axl in T-lymphocyte functions and its contribution to salt-dependent hypertension.
Approach and Results—We report increased apoptosis in peripheral blood from Axl−/− mice because of lower numbers of white blood cells mostly lymphocytes. In vitro studies showed modest reduction in interferon gamma production in Axl−/− type 1 T helper cells. Axl did not affect basic proliferation capacity or production of interleukin 4 in Axl−/− type 2 T helper cells. However, competitive repopulation of Axl−/− bone marrow or adoptive transfer of Axl−/− CD4+ T cells to Rag1−/− mice showed robust effect of Axl on T lymphocyte expansion in vivo. Adoptive transfer of Axl−/− CD4+ T cells was protective in a later phase of deoxycorticosterone-acetate and salt hypertension. Reduced numbers of CD4+ T cells in circulation and in perivascular adventitia decreased vascular remodeling and increased vascular apoptosis in the late phase of hypertension.
Conclusions—These findings suggest that Axl is critical for survival of T lymphocytes, especially during vascular remodeling in hypertension.
- Received March 7, 2016.
- Accepted June 20, 2016.
- © 2016 American Heart Association, Inc.