Activation of Th2 cells leads to Increased cellular proliferation and differentiation

The wound healing process involves an inflammatory phase, during which the damage tissue/wound is provisionally filled with extracellular matrix (ECM). This phase is characterised by secretion of cytokines/chemokines, growth factors and recruitment of inflammatory cells, fibroblasts and endothelial cells. The activated T helper (Th)1/Th2 response and increased pool of specific cytokines and growth factors such as Interleukin (IL)-1β, IL-6, IL-13, and Transforming growth factor beta (TGF-β), induce fibroblast proliferation. Th type 2 (Th2) cells can directly stimulate fibroblasts to synthesise collagen with IL-1 and IL-13. Th2 cytokines IL-13 and IL-4, known to mediate the fibrosis process induce phenotypic transition of human fibroblasts (Hashimoto et al., 2001). IL-13 is shown to inhibit Matrix metalloproteinases (MMP)-mediated matrix degradation resulting in excessive collagen deposition by downregulating the synthesis and expression of matrix degrading MMPs. IL-13 is also suggested to induce TGF-β1 in macrophages and its absence results in reduced TGF-β1 expression and decrease in collagen deposition (Fichtner-Feigl et al., 2006). These cytokines are suggested to initiate polarisation of macrophages to the alternative phenotype (M2). Th2 cells that synthesise IL-4 and IL-13 induce synthesis of Arginase (Arg)-1 in M2 macrophages. The Arg-1 pathway stimulates synthesis of proline for collagen synthesis required for fibrosis (Barron and Wynn, 2011).