γδ T cell–induced hyaluronan production by epithelial cells regulates inflammation

Abstract

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 γδ T cells play specialized roles in keratinocyte proliferation during wound repair. Here, we show that γδ 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 γδ 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 γδ T cells in inflammation and provide a new perspective on T cell regulation of ECM molecules.

Antigen-specific Vγ2Vδ2 T effector cells confer homeostatic protection against pneumonic plaque lesions

“…This finding implies that local production of tissue homeostatic factor FGF-7 by V␥2V␦2 T cells may be one of the potential mechanisms by which V␥2V␦2 T cells confer homeostatic protection against plague lesions. In this context, V␥2V␦2 T cells may also induce production of damage-resistant or healing molecules by epithelial cells as described (27).…”

Select Plant Tannins Induce IL-2Rα Up-Regulation and Augment Cell Division in γδ T Cells

“…Studies in animals show tissue ␥␦ T cells not only serve as effector cells, but also participate in immunoregulation (7), tissue homeostasis (2), and epithelial wound repair (48). Increasing these functions would directly and indirectly enhance host innate and downstream adaptive immune responses.…”

γδ T Cells Are Necessary for Platelet and Neutrophil Accumulation in Limbal Vessels and Efficient Epithelial Repair after Corneal Abrasion

“…Consistent with other organs, the ␥␦ T cells resident in the peripheral corneal and limbal surface are within the epithelium and, like those in the skin, 15 have a dendritic morphology (see Figure 1a). There is convincing evidence that the ␥␦ T cells in the skin, also called dendritic epidermal T cells, play a critical role in wound healing 15,41 and in the maintenance of epidermal integrity. 35,42,43 Dendritic epidermal T cells apparently recognize endogenous factors released or expressed on stressed or damaged epidermal cells 42,44 and are activated through ligation of the TCR.…”