Matrix remodelling and MMP expression/activation are associated with hidradenitis suppurativa skin inflammation

Abstract

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle, associated with considerable tissue remodelling. Although abnormal cytokine expression was detected both in perilesional and in uninvolved skin, up to now there is no model allowing a better understanding of the implicit inflammatory mechanisms in HS. The aim of this study was to investigate the inflammatory response in HS skin by mean of an ex vivo model culture. To that purpose, nine skin biopsy specimens from patients suffering from HS and controls were cultured up to 4 days. Microscopy imaging investigations showed variations of collagen I and III organization, and an increase in elastin fibres fragmentation in HS skin after 4 days of culture. The HS matrix structure remodelling was associated with high level of MMP‐2 and MMP‐9 in HS lesional skin. After 4 days of culture, the MMP expression in HS perilesional skin reached the level observed in HS lesional skin. Concomitantly, an increase in IL‐1β concentration was observed in all skin samples after 4 days of culture, although IL‐1β concentrations remained significantly higher in HS lesional skin as compared with control skin. Meanwhile, neither IL‐17 concentrations nor the inflammasome components NLRP3 and caspase‐1 varied. Thus, our HS skin model culture showed that MMP‐induced matrix alteration could participate in HS inflammation by releasing biological active peptides and inflammatory factors from the extracellular matrix (ECM), and open new opportunities to investigate the regulation of the inflammatory mechanism associated with HS.

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

“…Existing studies in HS demonstrate intriguing evidence of fibroblast‐related pathways being activated in lesional tissue. Elevations in IL‐1β, IL‐6, IL‐8, MMP2 and MMP9 as well as extensive matrix remodelling are core manifestations of HS . IHC studies have identified co‐localization of MMP2 to dermal fibroblasts .…”

“…HS significantly differs to other chronic inflammatory dermatose due to the development of hypertrophic scarring and dermal tunnels . The development of which suggest that fibroblastic stromal cells (including myofibroblasts, fibroblasts, pericytes etc) may be involved in the development and progression of disease . The recent investigations by Sanchez et al experimentally demonstrate that biologically active peptides and inflammatory mediators from the extracellular matrix (ECM) engage in inflammatory crosstalk with keratinocytes in HS.…”

“…The development of which suggest that fibroblastic stromal cells (including myofibroblasts, fibroblasts, pericytes etc) may be involved in the development and progression of disease . The recent investigations by Sanchez et al experimentally demonstrate that biologically active peptides and inflammatory mediators from the extracellular matrix (ECM) engage in inflammatory crosstalk with keratinocytes in HS. This paper begins to lay the foundation for future investigations into the interaction between ECM, fibroblasts and keratinocytes in HS.…”

Hidradenitis Suppurativa and 1-Carbon Metabolism: Role of Gut Microbiome, Matrix Metalloproteinases, and Hyperhomocysteinemia

“…Recently, Sanchez et al produced an ex-vivo cultured skin model for HS (25) and observed the specimens through immunohistochemistry. MMP-2 and MMP-9 were elevated in lesional skin.…”

New developments in hair research

“…These cells also express IL‐17 and IL‐23 which may support lymphocyte activation and/or changes to hair follicle biology . Innate cells, non‐immune cells, extracellular matrix remodelling, cytokines, chemokines and hormones in the vicinity may all have an impact on the development of lymphocytic scaring alopecias.…”