Aberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis

Area of Science:

• Immunology
• Dermatology
• Fibrosis Research

Background:

• Systemic sclerosis (SSc) is an autoimmune fibrotic disease with unclear mechanisms and limited treatments.
• Fibrosis in SSc affects skin and internal organs, leading to significant morbidity.

Purpose of the Study:

• To investigate the role of chitinase 3-like 1 (Chi3L1) in SSc pathogenesis.
• To identify potential therapeutic targets for SSc fibrosis.

Main Methods:

• Single-cell RNA sequencing of SSc skin cells.
• Analysis of Chi3L1 expression in SSc patients and a bleomycin-induced SSc mouse model.
• Investigating the mechanism of Chi3L1-mediated fibroblast activation.
• Evaluating the efficacy of IL-17RA antagonists.

Main Results:

• A subset of basal cells with high Chi3L1 expression was identified in SSc.
• Elevated Chi3L1 levels in SSc skin and serum correlated with disease severity.
• Chi3L1 promoted fibroblast to myofibroblast differentiation, worsening fibrosis.
• Chi3L1 deficiency ameliorated fibrosis in mice; IL-17RA antagonists showed anti-fibrotic effects.

Conclusions:

• Chi3L1 is a potential biomarker for SSc fibrosis.
• Chi3L1 and its receptor IL-17RA are promising therapeutic targets for SSc.