Wound Healing Society

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Immune Cell Activity In Human Cutaneous Wound Healing And Skin Scarring: A Multiple Time Point Immunohistochemical Study
Sara Ud-Din1, Douglas McGeorge2, Ardeshir Bayat1.
1University of Manchester, Manchester, United Kingdom, 2Nuffield Grosvenor Hospital, Chester, United Kingdom.

BACKGROUND Immune cells are involved in all aspects of the wound healing repair process including the initial haemostasis phase and their function in driving scar formation. It is thought that various immune cells including macrophages and T-cells, play a role in aberrant wound healing and the fibrotic process seen in scar formation in adult skin. Their link to abnormal healing has led to increased attention in the context of cutaneous repair. High numbers of immune cells have been found in hypertophic and keloid scars compared to normotrophic scars. Nevertheless, there is a paucity of evidence of their role and activity over time in acute cutaneous wound healing and normal skin scarring in humans. METHODS We utilised 5mm skin-biopsies taken from the upper arms of 62 healthy volunteers performed at multiple time points; at initial day 0 and at weekly intervals thereafter (weeks (W) 1,2,3,4,5,6,8). Detailed immunohistochemistry (IHC) was undertaken to evaluate the time course of immune cell recruitment in this human wound healing model. RESULTS Double staining for M2 macrophages using CD68/CD206 demonstrated a 127% increase in cell count from day 0 (uninjured intact skin) to week 5 (110, 250 respectively; p=0.02), with a subsequent 50% reduction to values closer to baseline by week 8 (125). We performed analysis on CD8 T cells and demonstrated a 82% increase in number from uninjured intact skin (64) to week 5 (117; p=0.03) where this plateaued thereafter to week 8 (109). The number of intraepidermal langerin+ Langerhans cells increased from uninjured intact skin (18) to week 4 (54) and reduced slightly by week 8 (42). CONCLUSIONS These findings could lead to further studies on mechanisms of immune cell localisation and may aid the discovery of novel therapeutic agents aimed at reducing immune cell numbers in pathological skin conditions.

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