Figure 6. Proposed mechanism of fibroblast activation in EoE.

Together, our model suggests that esophageal fibroblasts are stimulated by the EoE inflammatory milieu to produce extracellular matrix proteins and begin remodeling the ECM. This increases stiffness of the environment, leading to enhanced TGFβ signaling in fibroblasts. The increasing stiffness and cytokine response fully activates fibroblasts, which continue to produce α-SMA and extracellular matrix components, such as collagen and fibronectin, and contract their environment to further increase stiffness, giving rise to a positive feedback loop of fibroblast stimulation and activation.