Tissue Remodeling and Repair During Type 2 Inflammation

Tissue remodeling and repair following injury is an active immunologic and tissue regenerative process predicated upon a T helper type 2 (Th2) cell response. While typically associated with immunity to helminths or allergic inflammation, the Th2 response mediates tissue repair, acting to regulate inflammation while promoting the expression of wound healing genes and growth factors involved in tissue regeneration. However, if not appropriately regulated, Th2 responses can drive fibrosis, a pathologic condition where excess extracellular matrix and scar tissue are formed to fill the wound instead of newly regenerated tissue. In this chapter, we review how the Th2 immune responses are generated following injury, and the mechanism by which Th2 cytokines orchestrate wound healing. We focus on the immune cells (e.g., Th2 cells and alternatively activated macrophages) that direct this complex process, and the cytokines (e.g., IL-4 and IL-13) and growth factors (e.g., TGF-β) they secrete to mediate wound healing. Second, we detail the downstream wound healing pathways triggered by these factors notably tissue remodeling, extracellular matrix deposition and tissue regeneration. Finally, we discuss the clinical implications of the Th2 immune response on wound healing and fibrosis, and what key factors can be targeted to regulate the balance between optimal wound healing and detrimental fibrosis.