Figure 8. Endogenous glucocorticoids are required to maintain gastric homeostasis.

Under steady-state conditions, endogenous glucocorticoids suppress the expression of proinflammatory mediators in the gastric corpus. Loss of endogenous glucocorticoids results in the production of proinflammatory mediators, leading to infiltration of circulating monocytes and eosinophils. Infiltrating CX3CR1⁺ monocytes exhibit pathogenic activation due to disrupted glucocorticoid signaling, and damage the gastric epithelium, leading to SPEM development. Over the course of weeks, parietal cells are lost and the gastric gland becomes predominately filled with metaplastic cells which over time may create a favorable environment for the evolution of gastric adenocarcinoma.