Work

Mast cells at the crossroads of immune microenvironment remodeling in hypoxic pulmonary hypertension: a double-edged sword from degranulation to lipid mediators

Year: 2026

Type: article

Abstract: Hypoxic pulmonary hypertension (HPH) is characterized by persistent pulmonary vascular remodeling and elevated pressure, with immune microenvironment dysregulation driving its progression. Mast cells (MCs), as key innate immune cells, are activated under hypoxia via multiple pathways including ROS/calcium signaling, PI3K, and HIF-1α. Through degranulation, they release pro-inflammatory mediators such as histamine, IL-6, and TNF-α, while also secreting protective lipid mediators like ω-3 epoxides via non-degranulation pathways, thereby bidirectionally regulating vascular remodeling. Activated MCs interact with fibroblasts, macrophages, T cells, endothelial cells, and smooth muscle cells, exacerbating inflammation, immune imbalance, and extracellular matrix deposition through key signaling axes including IL-6, IL-1R1/MyD88, and RhoA-ROCK, thus promoting disease progression. Experimental strategies targeting MC stabilization, IgE-FcϵRIα signaling blockade, and the PAF-AH2-ω-3 epoxide axis have shown therapeutic efficacy. Future studies should utilize single-cell and spatial omics to dissect the spatiotemporal heterogeneity of cellular crosstalk and establish immune-phenotype-guided precision intervention systems, offering new directions for HPH therapy.

Source: Frontiers in Physiology

DOI: 10.3389/fphys.2026.1966811

Authors: Ting Zhai, Lan Ma

Institution: Qinghai University

Language: English

Topic: Pulmonary Hypertension Research and Treatments

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801