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Efficient macrophage migration into wounded skin requires hyaluronan (blue).

Specialized T cells in the skin lay a sugary foundation for macrophage migration into wounds, according to a study on page 1269. Jameson and colleagues show that the absence of dendritic epidermal γδ T cells (DETCs) removes the impetus for skin cells to secrete hyaluronan, an extracellular glycan that is required for macrophage entry into wounds. Without macrophages, wounds can't heal.Wound healing is initiated when DETCs recognize an unknown antigen on damaged skin cells. Neutrophils and, later, macrophages migrate to the wound site; both cell types are needed for complete healing. This group had previously shown that wound repair breaks down in the absence of DETCs due to a lack of keratinocyte growth factors FGF-7 and FGF-10, which are produced by DETCs in wounds and stimulate keratinocyte regeneration.

Jameson et al. noted that nonhealing wounds in DETC-deficient mice were less inflamed than normal wounds. They now show that, though neutrophils arrived at the wound on schedule, macrophages showed up late. The macrophage tardiness could be traced back to the lack of FGF-7. In normal wounds, FGF-7 was found to trigger the production of hyaluronan by neighboring keratinocytes and hyaluronan was needed to recruit macrophages. If hyaluronan (or FGF-7) was added back to the wounds, the macrophages returned and healing was restored.

Impaired wound healing is prevalent in patients with diabetes and rheumatoid arthritis. The authors hope to investigate whether impaired DETC function may be to blame in these human diseases.