# The Role of CCR10+ Regulatory T Cells In Hypertension

> **NIH NIH K08** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $158,436

## Abstract

Project Summary
 Hypertension is the leading cause of death and disability-adjusted life years worldwide. Despite current
therapies blood pressure remains uncontrolled in approximately 50% of individuals with hypertension, and even
with adequate control of BP an elevated risk of cardiovascular events remains. Hence, there is a major unmet
need for new therapeutic options for hypertension. Emerging evidence suggests an important role for the immune
system in the pathogenesis of hypertension. An immune cell subset termed regulatory T cells (Tregs) is an
attractive therapeutic target as it plays a suppressive role to limit inflammation. However, recent evidence
suggests that Tregs can play pathogenic roles in heart failure and lung fibrosis through inhibiting angiogenesis
and promoting fibrosis. Novel evidence provided with this application suggests that a subpopulation of Tregs
expressing C-C motif chemokine receptor 10 (CCR10) is selectively decreased in the circulation of hypertensive
humans and mice and is increased in the skin of mice with hypertension. Given recent evidence for an important
role for skin microvascular rarefaction (defined as loss of microvessels) in hypertension, these results suggest a
novel link between CCR10+ Tregs, skin microvessels, and hypertension development. To understand a
mechanism for these effects, we evaluated the effects of increased endothelial cell stretch, as occurs with
elevated blood pressure, on immune cells and found that CCR10+ Tregs are selectively increased with enhanced
endothelial stretch. Thus, studies in this application will test the hypothesis that increased endothelial cell stretch
augments CCR10 expression in Tregs and promotes CCR10+ Treg recruitment to the skin to enhance
microvascular rarefaction and hypertension development. This hypothesis will be tested with the following
specific aims: 1) to test the hypothesis that increased EC stretch enhances CCR10 expression in Tregs via tumor
necrosis factor alpha and to determine whether resultant CCR10+ Tregs transmigrate and inhibit angiogenesis
in response to CCR10 agonism by C-C motif chemokine ligand 27 (CCL27) in vitro, 2) to determine whether
CCR10+ Tregs promote skin microvascular rarefaction leading to elevated blood pressure in salt and angiotensin
II-induced hypertensive mouse models in vivo, and 3) to test whether CCR10 and its skin-specific ligand CCL27
promote hypertension in humans using a genetic approach of Mendelian randomization. Execution of the
outlined experiments will provide a platform for the applicant to gain further understanding and skills related to
the study of regulatory T cells and skin microvasculature as well as human genetic approaches such as
Mendelian randomization. This work will be performed at Vanderbilt University Medical Center which has
outstanding resources and mentorship to enable successful attainment of the career goals of the applicant,
namely to become an independent physician scientist caring for pa...

## Key facts

- **NIH application ID:** 10220135
- **Project number:** 5K08HL153786-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Matthew R Alexander
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $158,436
- **Award type:** 5
- **Project period:** 2020-07-20 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220135

## Citation

> US National Institutes of Health, RePORTER application 10220135, The Role of CCR10+ Regulatory T Cells In Hypertension (5K08HL153786-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10220135. Licensed CC0.

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