# Novel Role of Classical Dendritic Cells in the pathogenesis of Hypoxia-Induced Pulmonary Hypertension

> **NIH NIH K01** · UNIVERSITY OF COLORADO DENVER · 2024 · $132,299

## Abstract

ABSTRACT
Hypoxic Pulmonary hypertension (HPH) is characterized by elevated right ventricle pressures, increased
vascular remodeling and resistance, and it is often fatal. Dysregulated immunity underlies the
pathophysiology of the disease, which is supported by the elevated numbers of inflammatory cells around
the remodeled vessels, as well as high levels of inflammatory cytokines present in the plasma of patients
from different PH groups. Dendritic cells (DCs) are professional-antigen presenting cells that scan and
sense their tissue microenvironment, coordinating innate and adaptive immune responses. Classical
dendritic cells (cDCs) are divided in two different subsets: cDC1 (CD11b-/CD103+) and cDC2 (CD11b+).
Activated DCs modify their immediate tissue microenvironment by secreting chemokines and cytokines
that attract other inflammatory cells, including monocytes/ macrophages. Besides, activated cDCs drive
polarization of naïve T cells into different effector phenotypes, most importantly CD4+/Th17 cells, which
have been linked to experimental HPH. Therefore, there is a substantial body of evidence indicating that
dendritic cells are orchestrators of the PH-related immune response, including their augmented presence
around remodeled vessels in different etiologies of PH; however, there are few studies that address
pathogenic mechanisms in which these cells could participate in PH. Our preliminary data indicate that
bone-marrow-derived cDCs, particularly cDC2 that is increased in hypoxic PH lungs, are triggers of
hypoxia-induced HPH; that monocyte/ macrophage recruitment and Th17 polarization may be dependent
on cDC. The overall goal of this project is to determine the mechanistic role of the classical dendritic cell
subset cDC2, in driving the recruitment of pro-remodeling thrombospondin-1- expressing monocytes to
the lung, as well as directing T cell responses, which cause vascular remodeling in hypoxic pulmonary
hypertension (HPH). This project will be highly innovative in pulmonary vascular diseases and will serve
as a foundation to continue exploring this rich investigative research field, which will be essential to my
transition to an independent investigator.

## Key facts

- **NIH application ID:** 10914166
- **Project number:** 5K01HL161024-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Claudia Silva Mickael
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $132,299
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914166

## Citation

> US National Institutes of Health, RePORTER application 10914166, Novel Role of Classical Dendritic Cells in the pathogenesis of Hypoxia-Induced Pulmonary Hypertension (5K01HL161024-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10914166. Licensed CC0.

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