Figure 2.

Transforming growth factor‐β (TGF‐β) activated by integrins α _v β ₆ and α _v β ₈ has important functions at barrier sites. (a) Dendritic cells (DCs) are capable of activating latent TGF‐β through their expression of the integrin α _v β ₈, which modulates intestinal CD4⁺ T helper (Th) cell responses and Foxp3⁺ regulatory T (Treg) cells. In inflammatory bowel disease (IBD), α _v β ₈ expression is enhanced on DCs, whereas it is reduced on monocytes and macrophages. TGF‐β activation by integrin α _v β ₆ by intestinal epithelial cells (IECs) has been shown as a critical factor involved in the maintenance of intestinal tissue‐resident memory (Trm) cells. (b) In the lung, activation of TGF‐β by α _v β ₈‐expressing fibroblasts has been shown to drive DC chemotaxis. Moreover, integrin α _v β ₈‐expressing DCs appears to be required for the differentiation of Th17 cells. Integrin α _v β ₆‐mediated activation of latent TGF‐β by lung epithelial cells is a critical component of pulmonary homeostasis via preventing emphysema, whereas excessive TGF‐β signalling can facilitate pulmonary fibrosis in idiopathic pulmonary fibrosis (IPF) and promote infection. (c) Integrins α _v β ₆ and α _v β ₈ play an essential role in maintaining the cutaneous barrier in the skin. α _v β ₆‐mediated activation of latent TGF‐β by keratinocytes (KCs) is essential for re‐epithelialization and wound healing. Moreover, activation of latent TGF‐β by integrins α _v β ₆ and α _v β ₈ by KC in the epidermis are important for the maintenance of both Trm and Langerhans cells (LCs) in the skin. α _v β ₈ expression on regulatory T (Treg) cells is required to prevent overt effector T‐cell responses during acute inflammation. Migration of integrin α _v β ₈‐expressing DCs to skin‐draining lymph nodes is also important in imprinting CD8⁺ T cells to become CD8⁺ Trm cells.