Role of Axl in T-Lymphocyte Survival in Salt-Dependent Hypertension

Arterioscler Thromb Vasc Biol. 2016 Aug;36(8):1638-1646. doi: 10.1161/ATVBAHA.116.307848. Epub 2016 Jun 30.


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.

Keywords: Axl receptor tyrosine kinase; apoptosis; hypertension; lymphocyte; vascular remodeling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Apoptosis*
  • Axl Receptor Tyrosine Kinase
  • Blood Pressure*
  • CD4-Positive T-Lymphocytes / enzymology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Desoxycorticosterone Acetate
  • Disease Models, Animal
  • Genotype
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Hypertension / enzymology*
  • Hypertension / genetics
  • Hypertension / pathology
  • Hypertension / physiopathology
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lymphocyte Activation
  • Male
  • Mice, Knockout
  • Phenotype
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / deficiency
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Sodium Chloride, Dietary*
  • Time Factors
  • Vascular Remodeling


  • Homeodomain Proteins
  • Proto-Oncogene Proteins
  • Sodium Chloride, Dietary
  • RAG-1 protein
  • Interleukin-4
  • Desoxycorticosterone Acetate
  • Interferon-gamma
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL receptor tyrosine kinase, mouse