Other - eosinophilic esophagitis pathology
Eosinophilic esophagitis (EoE) is a chronic, allergic, inflammatory condition characterized by infiltration of eosinophils into the esophagus and symptoms such as dysphagia, food impaction, and vomiting. EoE is associated with a strongly enhanced mucosal T helper type 2 (Th2) cell response elicited by food allergens and subsequent production of pro-inflammatory cytokines and chemokines in esophageal tissue. IL-33 and IL-13 both contribute to EoE pathology (Travers J, et al. Sci Rep. 2017;7:17563; Blanchard C, et al. J Allergy Clin Immunol. 2007;120:1292-1300). In the present study, we assessed the effects of anti-IL-13 antibody treatment in a week-long, IL-33-mediated model of EoE in mice by thoroughly characterizing immune cell subsets in the esophagus using flow cytometry. Control mice with challenge developed marked esophageal inflammation and eosinophilic infiltration, similar to that observed in EoE patients. Furthermore, challenge promoted immune cell activation and production of pro-inflammatory cytokines in the esophagus, which was associated with tissue inflammation and remodeling. In addition to a dramatic infiltration of eosinophils, challenge led to a marked influx of ILC2 cells and to a lesser extent, T cells, dendritic cells, and macrophages. Measurements of systemic cytokines and chemokines in challenged animals also revealed enhanced levels of IL-13, IL-5, eotaxin, and periostin, important inflammatory mediators associated with human EoE. Administration of anti-IL-13 monoclonal antibodies to challenged mice significantly prevented esophageal eosinophilia and systemic inflammation. These findings confirm a pivotal role for IL-13 in promoting esophageal inflammation in a relevant model of EoE and the therapeutic potential of anti-IL-13 antibodies in EoE patients.