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

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Division of Nephrology
  • Duke University Medical Center

Details

Original languageEnglish (US)
Pages (from-to)869-876
Number of pages8
JournalHypertension
StatusPublished - Mar 1 2020
Peer-reviewedYes

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.

    Research areas

  • CCR7, blood pressure, dendritic cell, hypertension, lymph nodes

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Wen, Y, Rudemiller, NP, Zhang, J, Lu, X, Ren, J, Privratsky, JR, Griffiths, R, Zhang, JJ, Hammer, GE & Crowley, SD 2020, 'C-C Motif Chemokine Receptor 7 Exacerbates Hypertension through Effects on T Lymphocyte Trafficking', Hypertension, pp. 869-876. https://doi.org/10.1161/HYPERTENSIONAHA.119.14148