Hematopoietic prostaglandin D synthase: Linking pathogenic effector CD4+ TH2 cells to proeosinophilic inflammation in patients with gastrointestinal allergic disorders

Eosinophilic gastrointestinal disorders (EGIDs) are characterized as gastrointestinal disorders associated with overproduction of local T(H)2 cytokines, including IL-4, IL-5, and IL-13.(1) Although recent studies have identified multiple hematopoietic cell types to be involved in adverse allergic immune responses in the gastrointestinal tract, the primary cellular sources of T(H)2 cytokines and their interactions in the pathogenesis of EGIDs remain elusive.(1) Mechanistically, IL-4 secretion results in immunoglobulin class-switching to IgE in B cells(2) and induction of alternatively activated macrophages.(3) Production of IL-5 promotes the development, function, and survival of eosinophils,(4) and IL-13 induces dysregulated expression of epithelial cell-derived genes, including eotaxin 3,(5) desmoglein-1,(6) and LRRC31,(7) which have been shown to be involved in eosinophil recruitment and esophageal epithelial barrier functions. In addition, epithelial cell-derived T(H)2-promoting cytokines, including thymic stromal lymphopoietin (TSLP), IL-25, and IL-33, are likely to be potential mediators involved in the induction of gastrointestinal allergic diseases.(8,9)