Gammadelta T cell-induced hyaluronan production by epithelial cells regulates inflammation

Nonhealing wounds are a major complication of diseases such as diabetes and rheumatoid arthritis. For efficient tissue repair, inflammatory cells must infiltrate into the damaged tissue to orchestrate wound closure. Hyaluronan is involved in the inflammation associated with wound repair and binds the surface of leukocytes infiltrating damaged sites. Skin gammadelta T cells play specialized roles in keratinocyte proliferation during wound repair. Here, we show that gammadelta T cells are required for hyaluronan deposition in the extracellular matrix (ECM) and subsequent macrophage infiltration into wound sites. We describe a novel mechanism of control in which gammadelta T cell-derived keratinocyte growth factors induce epithelial cell production of hyaluronan. In turn, hyaluronan recruits macrophages to the site of damage. These results demonstrate a novel function for skin gammadelta T cells in inflammation and provide a new perspective on T cell regulation of ECM molecules.