Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages.

Dysregulated wound healing leads to fibrosis, whereby fibroblasts synthesize excess extracellular matrix and scarring impairs proper organ function. Although fibrotic diseases arise from diverse causes and display heterogeneous features, fibrosis commonly associates with chronic inflammation. Recent discoveries reinforce the idea that communication between fibroblasts, macrophages, and CD4 T cells integrates the processes of wound healing and host defense. Signals between macrophages and fibroblasts can exacerbate, suppress, or reverse fibrosis. Fibroblasts and macrophages are activated by T cells, but their activation also engages negative feedback loops that reduce fibrosis by restraining the immune response, particularly when the Th2 cytokine IL-13 contributes to pathology. Thus the interactions among fibroblasts, macrophages, and CD4 T cells likely play general and critical roles in initiating, perpetuating, and resolving fibrosis in both experimental and clinical conditions.