DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis

Area of Science:

• Oral pathology
• Stem cell therapy
• Immunology

Background:

• Oral submucous fibrosis (OSF) is a precancerous condition linked to betel nut use, characterized by fibrosis and inflammation.
• Current understanding of OSF pathogenesis is limited, leading to few effective treatments.
• Dental pulp stem cells (DPSCs) exhibit anti-inflammatory and anti-fibrotic properties, suggesting therapeutic potential for OSF.

Purpose of the Study:

• To elucidate the underlying cellular mechanisms driving oral submucous fibrosis (OSF).
• To investigate the therapeutic efficacy and mechanism of dental pulp stem cells (DPSCs) in treating OSF.

Main Methods:

• Single-cell RNA sequencing of human oral mucosal tissues to identify disease-specific cell populations and interactions.
• In vitro, in vivo (animal models), and clinicopathological validation of findings.
• Assessment of DPSC therapeutic effects using histological, immunohistochemical, scanning electron microscopy, and atomic force microscopy.

Main Results:

• A novel epithelial cell subtype (Epi1.2) with pro-inflammatory and pro-fibrotic functions was identified in OSF.
• Epi1.2 cells promote fibroblast activation via T cell interaction, involving MIF-CD74 and CXCR4 signaling.
• DPSCs demonstrated superior therapeutic effects in an OSF rat model compared to glucocorticoids, reducing collagen and enhancing vascularization.

Conclusions:

• Epithelial cell dysfunction and their crosstalk with T cells are key contributors to OSF pathogenesis.
• DPSCs offer a promising therapeutic strategy for OSF, modulating immune homeostasis and epithelial-stromal interactions.