Unraveling the ECM-Immune Cell Crosstalk in Skin Diseases

Abstract

The extracellular matrix (ECM) is a complex network of proteins and proteoglycans secreted by keratinocytes, fibroblasts and immune cells. The function of the skin ECM has expanded from being a scaffold that provides structural integrity, to a more dynamic entity that is constantly remodeled to maintain tissue homeostasis. The ECM functions as ligands for cell surface receptors such as integrins, dystroglycans, and toll-like receptors (TLRs) and regulate cellular signaling and immune cell dynamics. The ECM also acts as a sink for growth factors and cytokines, providing critical cues during epithelial morphogenesis. Dysregulation in the organization and deposition of ECMs lead to a plethora of pathophysiological conditions that are exacerbated by aberrant ECM-immune cell interactions. In this review, we focus on the interplay between ECM and immune cells in the context of skin diseases and also discuss state of the art therapies that target the key molecular players involved.

Role of the extracellular matrix in skin aging and dedicated treatment - State of the art

“…Treatment protocols (number of sessions, frequency, maintenance, mix of introduced substances, combination with cosmetics, and nutraceuticals even) have to be individualized in order to suit the patient's needs. Aesthetic dermatology is perhaps the first medical discipline dedicated towards studying the properties of ECM and its treatment but has increasingly, gained the attention of other clinical fields [28] such as orthopedics, dentistry, pulmonology and gastroenterology. We believe that in the near future, the ECM will be recognized as a master element of many organs and body systems, overcome the barriers and concepts of current specialty fields, and improve our mechanistic understanding of the many internal and external dysfunctions and disease states for better treatment.…”

The Extracellular Matrix in Skin Inflammation and Infection

“…The list shown is not comprehensive. Further details on ECM proteins and associated diseases have been summarized in Uitto et al (1989), Bosman and Stamenkovic (2003), Mouw et al (2014), Fidler et al (2018, Bhattacharjee et al (2019), Nystrom and Bruckner-Tuderman (2019). PG, proteoglycan; GAG, galactosaminoglycan/glycosaminoglycan; HS, heparan sulfate; BM, basement membrane; TSP-1, thrombospondin 1; FACIT, fibrilassociated collagens with interrupted triple helices; MACIT, membrane-associated collagens with interrupted triple helices; EB, epidermolysis bullosa, a severe skin disease that manifests in skin fragility and blistering (Bhattacharjee et al, 2019).…”

Notch-ing up knowledge on molecular mechanisms of skin fibrosis: focus on the multifaceted Notch signalling pathway

“…ECM works as a structural scaffold but also importantly as a biologically active system, able to modulate the behaviour of the surrounding cells and orchestrate a plethora of processes including cell proliferation, motility, differentiation, polarity and WH. Given its pleiotropic roles, ECM homeostasis is crucial for health maintenance [ 91 – 93 ]. Indeed, ECM architecture and composition are altered in multiple pathological conditions, including fibrosis [ 94 – 96 ].…”