Allergic skin sensitization promotes eosinophilic esophagitis through the IL-33–basophil axis in mice

Abstract

Epicutaneous allergic sensitization promotes EoE, and this is critically mediated through the IL-33-ST2-basophil axis.

Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

“…In addition to the above studies, Venturelli and colleagues employed additional murine models of EoE-like disease and have also found an important role for basophils in promoting esophageal inflammation. However, these pathways were dependent on the alarmin IL-33 rather than TSLP (145). These important murine studies are supported by human data demonstrating that increased expression of TSLP and IL1RL1/ST2 are found in the esophageal biopsies of patients suffering from EoE (145, 146).…”

“…However, these pathways were dependent on the alarmin IL-33 rather than TSLP (145). These important murine studies are supported by human data demonstrating that increased expression of TSLP and IL1RL1/ST2 are found in the esophageal biopsies of patients suffering from EoE (145, 146). Further, basophil populations have also been found to be significantly increased in esophageal biopsies taken from EoE patients (144).…”

Novel immunologic mechanisms in eosinophilic esophagitis

“…Mice genetically deficient in TSLP receptor or with TSLP neutralized are protected from experimental EoE [31 • ]. Additionally, leukocyte-intrinsic, competent IL-33 signaling is necessary for esophageal eosinophilia and type 2 cytokine induction [35], and intraperitoneal IL-33 administration is sufficient to induce esophageal eosinophilia and epithelial hyperplasia [36]. Collectively, the observation of their elevated epithelium-localized expression in EoE, genetic variant association with disease risk, and their requirement for select pathologic aspects of experimental EoE suggest that these cytokines likely have a key role in the initiation of EoE pathogenesis.…”

“…Basophils are observed to be increased in EoE [31 • ], colocalize with TSLP [32], and have increased ST2 expression [55]. In addition, an increased number of basophils are recruited to the esophagus in an ST2-dependent manner in a TSLP-dependent experimental EoE model, suggesting IL-33 may drive basophil recruitment to the esophagus [35]. Depletion of basophils prevents esophageal eosinophilia and induction of genes related to type 2 cytokine responses; furthermore, TSLP and basophils are required after disease establishment to maintain esophageal eosinophilia [31 • ].…”

La mystérieuse œsophagite à éosinophiles garde encore quelques secrets

“…Ce caractère non-essentiel aa ussi été suggéré chez des souris déficientes en IL-13, qui étaient résistantes dans un modèle expérimental classique d'EoE [38], ainsi que des souris traitées avec un anticorps anti-IL-13 (A. Vicari, données non publiées). Finalement, à ce profilc lassique Th2/éosinophiles, il convient d'ajouter d'autres populations de leucocytes fréquemment impliquées dans les réactionsi n fl ammatoiresa llergiques :l es basophiles et les mastocytes, qui pourraient jouer un rôle spécifique important dans la pathogénie de l'EoE [31,39,40], et peut-être permettre de distinguer l'EoE des formes d'éosinophilie oesophagienne répondante aux IPP [41].…”