Contribution of fibroblasts to tunnel formation and inflammation in hidradenitis suppurativa/ acne inversa

Abstract

The precise pathogenic mechanisms in the development, persistence and worsening of hidradenitis suppurativa (HS) remain ill-defined. This chronic inflammatory dermatosis displays a strong Th1 and Th17 inflammatory signature with elevated levels of TNF-α, IL-1β, IL-17 and IFNγ in lesional and perilesional tissue. HS significantly differs to other chronic inflammatory dermatoses due to the development of hypertrophic scarring and dermal tunnels. The development of scarring and tunnels suggests that fibroblastic stromal cells (including myofibroblasts, fibroblasts, pericytes etc) may be involved in the development and progression of disease. Heterogeneous populations of fibroblasts have been identified in other inflammatory disorders and malignancy which contribute to inflammation and present novel therapeutic targets for fibrotic disorders. Findings in HS are consistent with these fibroblast subpopulations and may contribute to tunnel formation, aggressive squamous cell carcinoma and the phenotypic presentation of familial HS variants. We describe the existing knowledge regarding these mechanistic pathways and methods to confirm their involvement in the pathogenesis of HS.

Keywords: acne inversa; fibroblasts; hidradenitis suppurativa; pathogenesis; scarring.

Figure 1:

Proposed Role for Fibroblasts in Tunnel Formation and Inflammation in Hidradenitis Suppurativa. Acute inflammation may act as a priming signal for the activation of fibroblasts through epigenetic mechanisms (1. Inflammatory Priming) leading to the emergence of four discrete subpopulations (2. FSC Subpopulations). Each subpopulation demonstrates specific functional characteristics via actions involving specific inflammatory mediators, transcription factors and cellular pathways (3. Cellular Interactions). Such interactions are associated with (and proposed to be mechanistic causative in) the development of tunnels, epithelialized tracts and fibrosis in HS (4. Resultant Tissue Effects).