Type 2 Inflammation and Fibrotic Pathways Drive Localized Scleroderma

A recent abstract published in the Journal of the American Academy of Dermatology underscores the pivotal role of adaptive immunity and type 2 inflammation in the development and progression of localized scleroderma (LS), with implications for targeted treatment strategies. Using high-throughput RNA sequencing, researchers compared inflammatory signatures in juvenile patients with LS and healthy controls, uncovering key immune pathways linked to disease activity and progression.

Analyzing data from 28 juvenile patients with LS and 10 healthy controls, the study identified 173 upregulated and 160 downregulated genes in patients with LS. Active LS showed pronounced upregulation of Th1, Th2, and Th17 pathways, along with elevated markers of eosinophil activity. In contrast, fibrotic LS stages were dominated by extracellular matrix and collagen formation genes, such as COL7A1 and COL4A5, as well as keratinization-related genes like KRT14 and KRT1.

Pathway analyses pinpointed interferon signaling, antigen presentation, and T-helper cell differentiation as central mechanisms in active LS. The study further correlated the histological and clinical activity of LS, demonstrating similar inflammatory signatures and reinforcing the role of type 2 immunity, particularly eosinophil involvement, in disease pathogenesis.

In fibrotic stages, collagen production and skin keratinization processes predominated, suggesting a transition from active inflammation to tissue remodeling and scarring. These findings provide valuable insight into LS’s immunological landscape, identifying adaptive immunity and fibrotic pathways as potential targets for future therapeutic interventions.

Reference
Khoury L, Prosty C, Osman M, Torok KS, Lefrançois P, Netchiporouk El. Markers of type 2 inflammation and immunosenescence are upregulated in localized scleroderma. J Am Acad Dermatol. 2024;91(3):AB62. doi:10.1016/j.jaad.2024.07.255