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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Wen, Y; Rudemiller, NP; Zhang, J; Lu, X; Ren, J; Privratsky, JR; Griffiths, R; Zhang, JJ; Hammer, GE; Crowley, SD

Published Date

  • March 2020

Published In

Volume / Issue

  • 75 / 3

Start / End Page

  • 869 - 876

PubMed ID

  • 31983306

Pubmed Central ID

  • PMC7035160

Electronic International Standard Serial Number (EISSN)

  • 1524-4563

Digital Object Identifier (DOI)

  • 10.1161/HYPERTENSIONAHA.119.14148

Language

  • eng

Conference Location

  • United States