Targeting the IFN-γ/CXCL10 pathway in lichen planus

Area of Science:

• Immunology
• Dermatology
• Oral Medicine

Background:

• Lichen planus is a chronic inflammatory condition affecting skin, nails, and mucous membranes.
• Oral lichen planus, particularly atrophic and erosive forms, presents significant management challenges due to limited treatment evidence.
• Cell-mediated cytotoxicity is a key pathogenic mechanism, with elevated interferon-gamma-induced chemokines CXCL10 and CXCL9 observed in patients.

Purpose of the Study:

• To explore the interferon gamma/CXCL10 axis as a therapeutic target for lichen planus.
• To investigate the potential of Janus kinase (JAK) inhibitors in managing lichen planus by blocking interferon gamma signaling.

Main Methods:

• Analysis of chemokine expression (CXCL10, CXCL9) in serum, skin, and mucosal lesions of lichen planus patients.
• Review of the role of the interferon gamma signaling pathway and its downstream effects.
• Evaluation of JAK inhibitors as a potential therapeutic strategy.

Main Results:

• Strong expression of CXCL10 and CXCL9 was detected in serum and lesions, highlighting the interferon gamma/CXCL10 axis's role.
• This axis is crucial for the progression and maintenance of chronic cytotoxic inflammation in lichen planus.
• Interferon gamma signaling involves JAK 1 and 2, suggesting JAK inhibitors can block this pathway.

Conclusions:

• The interferon gamma/CXCL10 axis represents a promising therapeutic target for reversing inflammation in lichen planus.
• JAK inhibitors offer a potential treatment strategy by inhibiting interferon gamma signaling and reducing CXCL10 expression.
• Further research into JAK inhibitors could lead to improved management of challenging oral lichen planus cases.