Chemokine ligand–receptor interactions critically regulate cutaneous wound healing

Abstract

BackgroundWound healing represents a dynamic process involving directional migration of different cell types. Chemokines, a family of chemoattractive proteins, have been suggested to be key players in cell-to-cell communication and essential for directed migration of structural cells. Today, the role of the chemokine network in cutaneous wound healing is not fully understood. Unraveling the chemokine-driven communication pathways in this complex process could possibly lead to new therapeutic strategies in wound healing disorders.MethodsWe performed a systematic, comprehensive time-course analysis of the expression and function of a broad variety of cytokines, growth factors, adhesion molecules, matrixmetalloproteinases and chemokines in a murine cutaneous wound healing model.ResultsStrikingly, chemokines were found to be among the most highly regulated genes and their expression was found to coincide with the expression of their matching receptors. Accordingly, we could show that resting and activated human primary keratinocytes (CCR3, CCR4, CCR6, CXCR1, CXCR3), dermal fibroblasts (CCR3, CCR4, CCR10) and dermal microvascular endothelial cells (CCR3, CCR4, CCR6, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3) express a distinct and functionally active repertoire of chemokine receptors. Furthermore, chemokine ligand–receptor interactions markedly improved the wound repair of structural skin cells in vitro.ConclusionTaken together, we here present the most comprehensive analysis of mediators critically involved in acute cutaneous wound healing. Our findings suggest therapeutic approaches for the management of wound closure by targeting the chemokine network.Electronic supplementary materialThe online version of this article (10.1186/s40001-017-0299-0) contains supplementary material, which is available to authorized users.

Tissue Iron Promotes Wound Repair via M2 Macrophage Polarization and the Chemokine (C-C Motif) Ligands 17 and 22

“…43 M2 macrophages release a myriad of factors (eg, transforming growth factor-b1) to promote reepithelialization, fibroplasia, fibroblast differentiation, 13 and ECM remodeling. 29 In the current study, it is shown, for the first time, that iron treatment of macrophages significantly potentiated the release of a range of chemokines, which promoted collagen production in HDFs. M2 macrophage CM is known to stimulate collagen 1 and collagen 3 production in fibroblasts in vitro, 44 but direct application of M2-stimulated BMDMs did not alter Db healing in vivo.…”

Pathogenic implication of epidermal scratch injury in psoriasis and atopic dermatitis

“…135 The keratinocyte-derived CCL20 in autocrine or paracrine manner binds CCR6 and upregulates migratory capacity of keratinocytes that may accelerate the Koebner phenomenon in psoriatic patients. 135 In IL-4/IL-13dominant AD, pruritus-mediated scratching induces CCL20 production from epidermal keratinocytes, which may explain why IL-17A-producing immune cells infiltrate atopic skin. However, the pathogenic role of IL-17A-producing immune cells in AD may be limited.…”

SingleCellSignalR: Inference of intercellular networks from single-cell transcriptomics

“…Interestingly, we noticed that LR pairs involved in wound healing regulation (54) were expressed by IFE K2 and D1 (Fig. 4I).…”