Immune cells and associated molecular markers in dermal fibrosis with focus on raised cutaneous scars

Raised dermal scars including hypertrophic, and keloid scars as well as scalp-associated fibrosing Folliculitis Keloidalis Nuchae (FKN) are a group of fibrotic raised dermal lesions that mostly occur following cutaneous injury. They are characterized by increased extracellular matrix (ECM) deposition, primarily excessive collagen type 1 production by hyperproliferative fibroblasts. The extent of ECM deposition is thought to be proportional to the severity of local skin inflammation leading to excessive fibrosis of the dermis. Due to a lack of suitable study models, therapy for raised dermal scars remains ill-defined. Immune cells and their associated markers have been strongly associated with dermal fibrosis. Therefore, modulation of the immune system and use of anti-inflammatory cytokines are of potential interest in the management of dermal fibrosis. In this review, we will discuss the importance of immune factors in the pathogenesis of raised dermal scarring. The aim here is to provide an up-to-date comprehensive review of the literature, from PubMed, Scopus, and other relevant search engines in order to describe the known immunological factors associated with raised dermal scarring. The importance of immune cells including mast cells, macrophages, lymphocytes, and relevant molecules such as cytokines, chemokines, and growth factors, antibodies, transcription factors, and other immune-associated molecules as well as tissue lymphoid aggregates identified within raised dermal scars will be presented. A growing body of evidence points to a shift from proinflammatory Th1 response to regulatory/anti-inflammatory Th2 response being associated with the development of fibrogenesis in raised dermal scarring. In summary, a better understanding of immune cells and associated molecular markers in dermal fibrosis will likely enable future development of potential immune-modulated therapeutic, diagnostic, and theranostic targets in raised dermal scarring.