IL‐13 From Murine Epidermal γδ T Cells Promotes Wound Healing by Inducing Arginase‐1‐Positive Hypodermal Macrophages in the Early Inflammatory Phase

ABSTRACT Murine epidermal γδ T cells, known as dendritic epidermal T cells (DETCs), play critical roles in cutaneous wound healing by secreting chemokines, cytokines and growth factors. Although DETCs predominantly produce IL‐13 early after activation, the specific role of DETC‐derived IL‐13 in wound repair remains unknown. Here, we show that periwound DETCs are the primary source of IL‐13 at early wound sites (4 h after full‐thickness skin wounding). The delayed wound closure in DETC‐deficient Tcrd −/− mice was restored by the local application of IL‐13 immediately after wounding. Previous studies have demonstrated that macrophages infiltrating the wound granulation tissue undergo a phenotypic shift from iNOS‐positive, proinflammatory type to arginase‐1‐positive, anti‐inflammatory type during the late inflammatory phase (3–5 days post injury). At 24 h post wounding, however, most macrophages infiltrating the periwound hypodermis expressed arginase‐1. In Tcrd −/− mice, both the number of macrophages in the periwound hypodermis and their arginase‐1 expression were significantly reduced. Local IL‐13 administration restored arginase‐1 expression in the hypodermal macrophages without altering their overall number in Tcrd −/− mice. These results indicate that IL‐13 rapidly produced by DETCs upon skin injury plays a critical role in wound healing by inducing arginase‐1‐positive macrophages in the periwound hypodermis during the early inflammatory phase.