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Germ-free, carefree: injured skin uses IL-24 to kick-start repair independent of pathogen-recognition

Signal Transduction and Targeted Therapy 2023年第11期8卷 5129-5131页

作者： Ruben A.Ferrer marta torregrossa Sandra Franz Department of Dermatology Allergology and VenerologyUniversity LeipzigLeipzigGermany

Skin injury releases damage-associated molecular patterns(DAMPs)represented by tissue-components and intracellular contents as well as changes in the levels of certain molecules and metabolites that signal the“non-homeostatic”state of the tissue.In addition,microorganisms entering a wound release molecules,which are sensed as“non-self”(pathogen-associated molecular patterns,PAMPs).Together,DAMPs and PAMPs initiate a complex and coordinated repair process aimed at restoring homeostasis.The exciting work from Liu et al.reports of an additional novel mechanism by which a“non-homeostatic”state in murine cutaneous wounds elicits a response through IL-24 to mediate repair(Fig.1).

关键词： wound homeostasis release

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Collagen/hyaluronan based hydrogels releasing sulfated hyaluronan improve dermal wound healing in diabetic mice via reducing inflammatory macrophage activity

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Bioactive Materials 2021年第12期6卷 4342-4359页

作者： Sophia Hauck Paula Zager Norbert Halfter Elke Wandel marta torregrossa Ainur Kakpenova Sandra Rother Michelle Ordieres Susann Räthel Albrecht Berg Stephanie Möller Matthias Schnabelrauch Jan C.Simon Vera Hintze Sandra Franz Department of Dermatology Venerology und AllergologyLeipzig University04103LeipzigGermany Institute of Materials Science Max Bergmann Center for BiomaterialsTechnische Universitǎt Dresden01069DresdenGermany Biomaterials Department INNOVENT e.V.JenaGermany

Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds.Control of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic strategies.Here we describe immunomodulatory hyaluronan/collagen(HA-AC/coll)-based hydrogels containing high-sulfated hyaluronan(sHA)as immunoregulatory component for the modulation of inflammatory macrophage activities in disturbed wound healing.Solute sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in vitro.This further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo cultures.In a mouse model of acute skin inflammation,intradermal injection of sHA downregulates the inflammatory processes in the skin.This is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation profile.For in vivo translation,we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one week.Their immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice,an established model for disturbed wound healing.The sHA-releasing hydrogels improved defective tissue repair with reduced inflammation,augmented pro-regenerative macrophage activation,increased vascularization,and accelerated new tissue formation and wound closure.

关键词： 4-6):sulfated hyaluronan Macrophages Immunomodulation Chronic wounds Hydrogel Skin inflammation

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