C-C Motif Chemokine Receptor 7 Exacerbates Hypertension Through Effects on T Lymphocyte Trafficking. Issue 3 (March 2020)

• Record Type: Journal Article
• Authors: Wen, Yi; Rudemiller, Nathan P.; Zhang, Jiandong; Lu, Xiaohan; Ren, Jiafa; Privratsky, Jamie R.; Griffiths, Robert; Zhang, Junyi J.; Hammer, Gianna E.; Crowley, Steven D.
• Is Part Of: Hypertension. Volume 75:Issue 3(2020)
• Publication Date: 2020-03
• Subjects: blood pressure -- CCR7 -- dendritic cell -- hypertension -- lymph nodes; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.119.14148
• Languages: English
• ISSNs: 0194-911X

Abstract

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. Abstract : Supplemental Digital Content is available in the text.