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

Hypertension 2020 Mar 27;75(3):869-876. Epub 2020 Jan 27.

From the Division of Nephrology, Department of Medicine, Durham VA and Duke University Medical Center, NC (Y.W., N.P.R., J.Z., X.L., J.R., R.G., S.D.C.).

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.

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Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035160PMC
March 2020
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References

(Supplied by CrossRef)
Hypertension among adults in the united states: national health and nutrition examination survey, 2011-2012.
Nwankwo T et al.
NCHS Data Brief 2013

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