Fig. 6.

A schematic view of the fibrotic response. The innate and adaptive immune systems are activated at the tissue repair stage. The pro-inflammatory chemokines and cytokines secreted by macrophage cells trigger the inflammatory recruitment process. TGFβ1, IL-17, and IL-18 from immune cells promote fibroblast proliferation and transformation. In addition, type I and type II immunity are cross-activated for defense and metabolic homeostasis maintenance. The adaptive immune CD4⁺ Th2 cell can directly activate fibroblasts by IL-4 and IL-21, independent of TGFβ1 induced fibrosis. Excessive ECM deposition leads to fibrosis ultimately. ECM extracellular matrix, EMT epithelial-to-mesenchymal transition, IL interleukin, ILC2 group 2 innate lymphoid cells, MMP matrix metalloprotease, Th2 T helper 2, TGFβ1 transforming growth factor β1, TNF tumor necrosis factor