Figure 1.

Overview of wound repair and fibrosis. Epithelial and/or endothelial damage caused by various insults triggers complex interconnected wound-healing programs to quickly restore homeostasis. The coagulation pathway, which functions to stem blood loss, is triggered first, followed by acute inflammation and activation of innate immune mediators such as resident macrophages, neutrophils and dendritic cells. Epithelial and innate immune cell–derived cytokines subsequently influence the activation of the adaptive immune response. The tissue damage can also directly activate the adaptive immune response. Inflammatory and immune mediators (cytokines, chemokines and free radicals) attempt to eliminate the inciting factor while activating the resident quiescent fibroblasts into myofibroblasts that orchestrate angiogenesis and production of ECM components. Failure to adequately contain or eliminate the inciting factors can exacerbate the inflammatory response and lead to a chronic wound-healing response, with continued tissue damage, repair and regeneration, ultimately resulting in fibrosis. TSLP, thymic stromal lymphopoietin; Ab, antibody; PMN, polymorphonuclear leukocyte; EOS, eosinophil; Baso, basophil; Mast, mast cell.