Insights into the role of fibroblasts in human autoimmune diseases

Abstract

Traditional wisdom has considered fibroblasts as contributing to the structural integrity of tissues rather than playing a dynamic role in physiological or pathological processes. It is only recently that they have been recognized as comprising diverse populations of cells exhibiting complex patterns of biosynthetic activity. They represent determinants that react to stimuli and help define tissue remodelling through the expression of molecules imposing constraints on their cellular neighbourhood. Moreover, fibroblasts can initiate the earliest molecular events leading to inflammatory responses. Thus they must now be viewed as active participants in tissue reactivity. In this short review, I will provide an overview of contemporary thought about the contribution of fibroblasts to the pathogenesis of autoimmune processes through their expression of, and responses to, mediators of inflammation and tissue remodelling.

Fig. 1

Schematic of the phenotypic attributes exhibited by Type B synovial fibroblasts and how they are believed to interact with recruited immunocompetent cells in rheumatoid arthritis.

Fig. 2

Some fibroblasts, like those from the orbit, can differentiate into different cell types. Thy-1⁺ fibroblasts, when treated with transforming growth factor (TGF)-β, can differentiate into myofibroblasts that express high levels of α-smooth muscle specific actin. Thy-1⁻ fibroblasts treated with PPARγ agonists, accumulate triglycerides and exhibit the phenotype of adipocytes.

Fig. 3

Schematic of the phenotypic attributes of orbital fibroblasts and how they are thought to interact with immunocompetent cells recruited to the orbit in thyroid-associated ophthalmopathy (TAO).