Additional file 5: of T-cell costimulation blockade is effective in experimental digestive and lung tissue fibrosis

Abatacept alleviates inflammation-driven fibrosis by suppressing the immune response. Schematic cartoon of the mechanism of action of abatacept in systemic sclerosis (SSc) based on results presented in this study and previously published results in skin fibrosis [5]. In the early stages of SSc, T cells are activated through their TCR and receive costimulation via CD28 from CD80/CD86-expressing antigen-presenting cells. The full activation of T cells enhances the activation of dermal/lung fibroblasts through the action of proinflammatory and/or profibrotic cytokines (IL-6, IL-10). This also involves the proinflammatory action of macrophages. During abatacept treatment, the drug blocks CD80/CD86-mediated costimulation by macrophages and B cells, leading to inhibition of T-cell activation, proliferation, and/or infiltration. The effects on macrophages lead to lower maturation and infiltration. B-cell infiltration is also reduced. As a consequence of the effect on T cells, B cells, and macrophages, the progression of dermal, lung, and vessel fibrosis is blocked. (TIFF 1546 kb