Inflammation drives wound hyperpigmentation in zebrafish by recruiting pigment cells to sites of tissue damage

Abstract

SUMMARYIn humans, skin is the largest organ and serves as a barrier between our body and the outside world. Skin protects our internal organs from external pathogens and other contaminants, and melanocytes within the skin protect the body from damage by ultraviolet light. These same pigment cells also determine our skin colour and complexion. Skin wounding triggers a repair response that includes a robust recruitment of inflammatory cells, which function to kill invading microbes and clear away cell and matrix debris. Once at the wound site, these innate immune cells release a barrage of cytokines that direct the activities of other cells during the repair process. Tissue damage and repair also frequently lead to alterations in skin pigmentation, in particular to wound hyperpigmentation. In this study, we describe a model of wound hyperpigmentation in the translucent zebrafish larva, where we can live-image the recruitment of melanocytes and their precursors, melanoblasts, to the wound site. We show that these pigment cells are drawn in after the initial recruitment of innate immune cells and that the inflammatory response is essential for wound hyperpigmentation. This new model will allow us to uncover the molecular link between immune and pigment cells during tissue repair and to screen for potential therapeutics to dampen wound hyperpigmentation.

Transcriptome analyses of differential gene expression in the bursa of Fabricius between Silky Fowl and White Leghorn

“…Therefore, the differentially expressed lncRNAs and microRNAs could regulate gene expression and modulate different biological processes. In the BF of SF, the melanocyte migration and proliferation was accompanied by aberrant B-cell development in a manner similar to the melanocyte migration and function at the site of injury in zebrafish9; however, this conclusion requires further study for verification.…”

Repigmentation of cutaneous scars depends on original wound type

“…; Lévesque et al. ). In particular, these studies have highlighted the potential immune‐modulatory function of melanocytes, provoking an inflammatory response in the very early stages of wound healing, and provided further information about melanocyte migration and patterning within skin (Takahashi & Kondo, ; Feng et al.…”

“…; Lévesque et al. ). Although most dyspigmentation states may be attributed to problems with melanogenesis, this is not always the case.…”

“…By contrast, Breathnach could not identify melanocytes in the centre of mid-dermal human scars, proposing instead that melanocytes migrated into a pre-formed sheet of epithelium after the wound had healed. In more recent years, other models such as zebrafish have been used in wound healing research, which has yielded further information about potential roles of melanocytes, other than as pigment-producing cells (Plonka et al 2009;L evesque et al 2012). In particular, these studies have highlighted the potential immune-modulatory function of melanocytes, provoking an inflammatory response in the very early stages of wound healing, and provided further information about melanocyte migration and patterning within skin (Takahashi & Kondo, 2008;Feng et al 2010;L evesque et al 2012).…”

Myeloid Cells in Cutaneous Wound Repair

“…Melanocytes and their undifferentiated precursors (melanoblasts) migrate to the wound site after neutrophil and Mϕ recruitment. Myeloid cell depletion in zebrafish results in reduced wound pigmentation through reduced melanocyte and melanoblast recruitment, suggesting that wound hyperpigmentation is driven by the inflammatory response (133). Future studies will hopefully study the signals produced by wound myeloid cells and how these regulate melanocyte recruitment.…”