Wednesday, November 23, 2016
Allergic skin sensitization promotes eosinophilic esophagitis through the IL-33–basophil axis in mice
Eosinophilic esophagitis (EoE) is an allergic disorder seen in approximately 1 out of 2000 people in the United States. Young children often present with vomiting and failure to thrive, while older children and adults may have difficulties swallowing, food impaction, or strictures in their esophagus. Despite increasing awareness and diagnosis, the etiology remains unclear. Past studies support the role of a subset of Helper T-cells, called TH2 cells, which are also present in many other allergic diseases, including atopic dermatitis (AD). In fact, approximately half of patients with EoE have AD. But why is that so?
In this month’s issue of the Journal of Allergy and Clinical Immunology, Venturelli and colleagues investigate the role of abnormal skin barriers in the development of EoE, and, in particular, the role of IL-33, a chemical messenger whose levels are elevated in both EoE and AD (J Allergy Clin Immunol 2016; 138(5): 1367-1380). They also investigated the role of ST2, an IL-33 receptor found on basophils using a mouse model. They applied ovalbumin to the mechanically injured skin of wild-type mice, and then to the skin of mice lacking filaggrin (ft/ft), which tend to develop AD-like skin lesions. They then challenged both strains of mice with intra-nasal ovalbumin. The esophagi of these mice were then examined microscopically and through advanced genetic analytic techniques.
They found that a disrupted skin barrier (by tape stripping or a Filaggrin gene mutation) promotes the development of EoE, and that this is mediated by IL-33, ST2, and basophils. They also reported that patients with EoE have increased ST2 in their esophagus. Their findings suggest that IL-33 could be a potential link between AD and EoE. This is an important step in understanding how patients with AD and filaggrin deficiency tend to develop EoE. Just as importantly, it may prompt development of new medications that block IL-33 or ST2, which could be effective targets for EoE.