Keloids and hypertrophic scars represent pathological cutaneous scars. They emerge from excessive wound healing, generating chronic dermal inflammation and overwhelming fibroblast production of extracellular matrix. However, their etiology remains unclear. 

Inflammasomes are multiprotein complexes that are critical in proinflammatory innate-immune system responses. 

A recent study examined whether inflammasomes participate in pathological scarring by reviewing the literature on scarring, diabetic wounds (also characterized by chronic inflammation) and systemic sclerosis (also marked by fibrosis). It found that pathological scars predominantly have anti-inflammatory M2 macrophages, and recent evidence suggests that this could be driven by noncanonical inflammasome signaling. Diabetic-wound healing is associated with inflammasome activation in immune (macrophages) and nonimmune (keratinocytes) cells. Fibrotic conditions link with inflammasome activation and inflammasome-induced transition of epithelial cells/endothelial cells/macrophages into myofibroblasts that deposit excessive extracellular matrix. Studies indicate that mechanical stimuli activate inflammasomes via the cytoskeleton and the involvement of mechanotransduction-inflammasome crosstalk in fibrosis.

Thus, further research should investigate (i) the roles of various inflammasome types in macrophages, (myo)fibroblasts and other cell types in keloid development and (ii) the interaction of mechanical stimuli with inflammasomes and scar growth promotion. Such research will help us understand pathological scarring and to develop new therapeutic strategies.

Source: Huang C, Ogawa R. Role of inflammasomes in keloids and hypertrophic scars-lessons learned from chronic diabetic wounds and skin fibrosis. Int J Mol Sci. 2022;23(12):6820.