Fibrosis and Autoimmune Diseases: Molecular, Immunological, and Epigenetic Drivers

10 Apr 20264 min read0 viewsJournal Feed

GIST (Key Takeaways)

Fibrosis is a pathological process of wound healing, characterized by excessive deposition of extracellular matrix (ECM) and chronic activation of fibroblasts, leading to organ scarring and a decline in function. Fibrogenesis is predominantly initiated by tissue injury and sustained inflammation, further driven by the complex interplay of growth factors, cytokines, metabolic alterations, and epigenetic reprogramming. Activated myofibroblasts and immune cells function as primary profibrotic mediators.
The central molecular pathways implicated include TGF-β/SMAD signaling, non-canonical cascades such as RAS-ERK and PI3K-AKT-mTOR, and integrin-mediated mechanotransduction. These pathways collectively contribute to matrix disruption by upregulating α-SMA, collagen, lysyl oxidase, and tissue inhibitors of metalloproteinases (TIMPs). Alterations in noncoding RNAs and histone/DNA modifications stabilize genes responsible for pro-fibrotic pathways, whereas metabolic reprogramming sustains myofibblast activity.
These mechanisms contribute to fibrosis in several autoimmune disorders, including rheumatoid arthritis, multiple sclerosis, Sjögren’s disease, and Crohn’s disease. In these conditions, persistent immune activation drives continuous crosstalk between immune cells and stromal fibroblasts, sustaining cytokine signaling and ECM remodeling. Current therapeutic approaches primarily aim to halt disease progression; however, achieving true reversal remains challenging.

Clinical Editorial

Frontiers in Immunology published a clinical update in Infectious Disease on 10 Apr 2026.

The item focuses on An intricate relationship between fibrosis and autoimmune diseases: a specific focus on unraveling its molecular, immunological, and epigenetic drivers.

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