C-C motif Chemokine Receptor 7 Exacerbates Hypertension through Effects on T Lymphocyte Trafficking
| Autor: | Xiaohan Lu, Nathan P. Rudemiller, Yi Wen, Steven D. Crowley, Jamie R. Privratsky, Jiafa Ren, Gianna E. Hammer, Junyi J. Zhang, Robert Griffiths, Jiandong Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Adoptive cell transfer Receptors CCR7 Lymphocyte Genes RAG-1 C-C chemokine receptor type 7 chemical and pharmacologic phenomena 030204 cardiovascular system & hematology Adaptive Immunity Kidney Nephrectomy Article 03 medical and health sciences Mice 0302 clinical medicine T-Lymphocyte Subsets Internal medicine Internal Medicine medicine Animals Lymph node Mice Knockout Chemistry Angiotensin II hemic and immune systems Dendritic cell T lymphocyte Dendritic Cells Adoptive Transfer Mice Inbred C57BL Chemotaxis Leukocyte 030104 developmental biology medicine.anatomical_structure Endocrinology Hypertension Lymph Lymph Nodes CD8 |
| Zdroj: | Hypertension |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|