Th9-endothelial cell crosstalk promotes inflammatory atherosclerotic cardiovascular disease

Area of Science:

• Immunology
• Cardiovascular Science
• Dermatology

Background:

• Atherosclerotic cardiovascular disease (ASCVD) is a major cause of mortality, with inflammation playing a key role.
• Patients with inflammatory conditions like psoriasis have an elevated risk of ASCVD.
• The specific inflammatory mediators driving ASCVD remain incompletely understood.

Purpose of the Study:

• To investigate the role of T helper 9 (Th9) cells and interleukin-9 (IL-9) in the pathogenesis of inflammatory atherosclerosis.
• To explore the potential of targeting the IL-9 pathway for ASCVD prevention and treatment.

Main Methods:

• Analysis of Th9 cell association with ASCVD in psoriasis patients.
• In vivo studies using murine models of inflammatory atherogenesis.
• In vitro studies on human arterial endothelial cells assessing IL-9 receptor (IL-9R) signaling.

Main Results:

• Th9 cells were significantly associated with ASCVD in psoriasis patients and found in atherosclerotic plaques.
• IL-9 blockade and IL-9R deletion in endothelial cells prevented murine inflammatory atherogenesis.
• IL-9R/STAT3 signaling in human endothelial cells promoted dysfunction, angiogenesis, and chemoattractant release.

Conclusions:

• Th9 cells and IL-9 directly promote atherosclerosis by targeting endothelial cells, particularly in the context of autoimmune diseases like psoriasis.
• The IL-9R/STAT3 signaling pathway represents a potential therapeutic target for ASCVD.