Study of the crosstalk between fibroblasts, eosinophils, and epithelial cells in a model of gastrointestinal eosinophilic disease

JULIÁN VACCARO; MANUELA ILID; MARÍA BELEN POLO; LORENA MENENDEZ; PAULA BOROBIA; CECILIA ZUBIRI; ANABELA ZOSI; LUCIANA GUZMÁN; VIVIANA BERNEDO; MARCELA GARCÍA; EUGENIA M ALTAMIRANO; JULIETA ARGUERO; JUAN ANDRÉS DE PAULA; LAURA UDABE; CECILIA ISABEL MUGLIA; RENATA CURCIARELLO; GUILLERMO DOCENA

Copenague

Congreso; International Congress of Mucosal Immunology 2024; 2024

Society for Mucosal Immunology

Eosinophilic Gastrointestinal Diseases (EoGD) are a group of pathologies distinguished by a predominant eosinophilic infiltration in different sections of the gastrointestinal tract. In these disorders, eosinophils are recruited to the lamina propria in an inflammatory context dominated by type 2 cytokines. However, the underlying molecular mechanisms remain unclear. This study aims to characterize cellular and molecular interactions between intestinal fibroblasts, eosinophils and epithelial cells from biological samples of patients with food allergy (FA) and Eosinophilic Esophagitis (EoE).Caco-2 and EPC-2 cells were stimulated with rh-IL-13, rh-IL-4, or rh-IFN-γ, and CCL26 was measured in culture supernatants. Eosinophils from FA polyps were sorted and cultured with IL-5. FA intestinal fibroblasts were also cultured and characterized. IL-8 and CCL26 were assessed after stimulation with rh-IL-13, rh-IL-4, rh-IL-9, rh-TGF-β, and eosinophil-conditioned media. EoE was studied in esophageal biopsies using IF staining for histological characterization and IgE detection, while the mucosal response to type 2 cytokines was examined ex-vivo in organ culture.Type 2 cytokines induced the CCL26 secretion on colonic and esophagus epithelial cells and FA polyp fibroblasts. The conditioned medium of sorted and cultured eosinophils from FA polyps activated intestinal fibroblasts. Mucosal sections of EoE adult patients exhibited elevated TSLP, CCL26, and α-SMA expression (activation fibroblast marker) but no IgE, with CCL26 and TSLP secretion following ex-vivo stimuli.In conclusion, we showed that epithelial cells and fibroblasts were involved in the secretion of chemokines and alarmins that could drive the recruitment of eosinophils in EoGD.