C-C Motif Chemokine Receptor 7 Exacerbates Hypertension Through Effects on T Lymphocyte Trafficking

Hypertension. 2020 Mar;75(3):869-876. doi: 10.1161/HYPERTENSIONAHA.119.14148. Epub 2020 Jan 27.

Abstract

Activated T lymphocytes that infiltrate blood pressure control organs make a critical contribution to the pathogenesis of hypertension. Dendritic cells act as potent antigen-presenting cells to stimulate prohypertensive T cells. However, the mechanisms that facilitate the recruitment of prohypertensive T cells and dendritic cells into the kidney's draining lymph node during hypertension require elucidation. As CCR7 (C-C motif chemokine receptor type 7) directs the homing of lymphocytes and dendritic cells into lymph nodes, we posited that dendritic cell-mediated T lymphocyte stimulation in the renal lymph node is CCR7 dependent and required for a full hypertensive response. We found that CCR7-deficient (CCR7 KO) mice had a blunted hypertensive response in our model of chronic Ang II (angiotensin II) infusion. Ang II-infused CCR7 KO animals had exaggerated accumulation of CD8+ T cells in the kidney but reduced numbers of CD4+ and CD8+ T cells in the kidney's draining lymph node. To understand whether CCR7-dependent homing of T lymphocytes or dendritic cells into the lymph node regulates the hypertensive response, we injected CCR7 KO or wild-type T cells or dendritic cells into CCR7 KO recipients, neither of which restored the full hypertensive response to Ang II infusion. However, adoptive transfer of wild-type but not CCR7 KO T lymphocytes into RAG1 (recombination-activating gene 1)-deficient mice that lack a lymphocyte niche restored full blood pressure elevation during Ang II infusion. Thus, CCR7-dependent interactions between T lymphocytes and dendritic cells are essential for T lymphocyte stimulation and hypertension accruing from inappropriate activation of the renin-angiotensin system.

Keywords: CCR7; blood pressure; dendritic cell; hypertension; lymph nodes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity
  • Adoptive Transfer
  • Angiotensin II / toxicity
  • Animals
  • Chemotaxis, Leukocyte / physiology*
  • Dendritic Cells / transplantation
  • Genes, RAG-1
  • Hypertension / immunology*
  • Hypertension / physiopathology
  • Kidney / immunology
  • Kidney / physiopathology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephrectomy
  • Receptors, CCR7 / deficiency
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / physiology*
  • T-Lymphocyte Subsets / immunology*

Substances

  • Ccr7 protein, mouse
  • Receptors, CCR7
  • Angiotensin II