Targeting the IL-6-Th17-Neutrophil Axis Reduces Local Inflammation in Stomatitis

Area of Science:

• Immunology
• Oral Pathology
• Inflammation Research

Background:

• Recurrent aphthous stomatitis (RAS) is a prevalent chronic oral condition with poorly understood causes.
• Chronic inflammation in RAS is associated with disrupted local immune responses.
• Understanding the immune microenvironment is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the immune changes in a chemical stomatitis (CS) mouse model.
• To elucidate the role of the IL-6-Th17-neutrophil axis in stomatitis pathogenesis.
• To explore potential immunotherapeutic targets for stomatitis.

Main Methods:

• Acetic acid-induced chemical stomatitis (CS) in a murine model.
• Flow cytometry to analyze immune cell populations (neutrophils, Th1, Th17).
• Genetic depletion of Th17 cells (Rorc-/- mice) and IL-6 receptor signaling (Il6ra-/- mice).
• Anti-Ly6G antibody treatment to deplete neutrophils.
• Histopathological analysis (Hematoxylin and eosin staining) for tissue damage assessment.

Main Results:

• CS mice showed increased neutrophil infiltration and elevated Th1/Th17 cells in lingual mucosa.
• Depletion of Th17 cells (Rorc-/-) reduced neutrophil infiltration and tissue damage.
• Impaired IL-6 receptor signaling (Il6ra-/-) decreased inflammatory cell infiltration and ulcer severity.
• Neutrophil depletion diminished Th1/Th17 cell infiltration, indicating a feedback loop.

Conclusions:

• The IL-6-Th17-neutrophil axis is a key driver of stomatitis pathogenesis.
• This axis creates a positive feedback loop between Th17 cells and neutrophils.
• Targeting this axis presents a promising immunotherapeutic strategy for stomatitis.