D1.157 - Type II Cytokine-Mediated Regulation of Alarmin Receptors in B Cells: Implications for Eosinophilic Esophagitis
Background
The regulation of B cell function by type II cytokines represents a potential contributor to immune-mediated disorders, including eosinophilic esophagitis (EoE). While EoE is characterized by eosinophilic infiltration in the esophagus, recent findings implicate B cells in its pathophysiology, as evidenced by elevated B cell counts and food-specific IgG4 antibodies in patients. However, the precise mechanisms by which type II cytokines influence B cell function, particularly through the regulation of alarmin receptors, remain poorly understood. This study aims to investigate how type II cytokines and associated activation stimuli modulate alarmin receptor expression on B cells, elucidating their potential contribution to EoE pathogenesis.
Method
B cells were purified from peripheral blood mononuclear cells (PBMCs) and tonsil tissue of healthy donors. In addition immortalized B cells derived from PBMCs of healthy donors and esophageal tissue of EoE patients we analyzed. Cells were treated with IL-4 and other type II cytokines in combination with activation factors such as CD40L, CpG, and BCR crosslinkers. Alterations in B cell phenotype and function were assessed using qPCR, ELISA, Olink proximity extension assay, and flow cytometry.
Results
Type II cytokines elicited variable effects on B cell receptor expression. CD40L and IL-4 co-stimulation significantly increased the expression of type II cytokine receptors, such as IL-4R and IL-13RA1, as well as IL-17RB, which may mediate IL-25 signaling. These findings suggest that type II cytokines influence alarmin receptor regulation, potentially altering B cell function in inflammatory conditions.
Conclusion
This study highlights the modulatory effects of type II cytokines on alarmin receptor expression in B cells, providing insights into their potential role in EoE pathogenesis. Future investigations are necessary to clarify the mechanisms underlying these interactions and their relevance as therapeutic targets.
