A systemic myeloid-driven Th1 hyper-response characterizes inflammatory oral ulceration

Area of Science:

• Immunology
• Oral Medicine
• Dermatology

Background:

• Recurrent aphthous stomatitis (RAS) and Behçet's oral lesions significantly reduce quality of life.
• Systemic Th1 polarization and myeloid mediator involvement in oral ulcers remain unclear.
• Existing treatments for Behçet's disease do not specifically target isolated oral ulcers.

Purpose of the Study:

• To investigate the systemic Th1 immune response in inflammatory oral ulcers.
• To identify correlations between Th1 markers and ulcer severity.
• To explore the role of myeloid cells in the pathogenesis of oral ulcers.

Main Methods:

• Plasma cytokine arrays and peripheral blood mononuclear cell (PBMC) flow cytometry were performed on 35 ulcer patients and 30 controls.
• Functional assays assessed the impact of cytokines on human oral keratinocytes (HOK).
• The Oral Ulcer Severity Score (OUSS) was used to correlate Th1 markers with clinical severity. Longitudinal changes after topical steroid treatment were monitored in a pilot cohort.

Main Results:

• Patients with inflammatory oral ulcers exhibited a dominant systemic Th1 signature, including elevated IFN-γ, TNF-α, and IL-12, with expanded T-bet+ CD4+ T cells.
• Activated CD14+ monocytes were identified as a source of IL-12.
• Elevated T-bet+ CD4+ T cells and IFN-γ levels significantly correlated with OUSS and ulcer size, respectively. Treatment reduced OUSS and Th1 markers.

Conclusions:

• Systemic Th1 hyperactivity, initiated by myeloid cells, is a key feature of inflammatory oral ulcers, contributing to epithelial injury.
• The Th1 pathway is a promising target for precision therapies aimed at inflammatory oral ulcers.
• Further research is needed to confirm causal relationships and optimize treatment strategies.