E‐selectin induction by IL‐1 and IFN‐ γ in the pathogenesis of type III immune hypersensitivity

Abstract

Erythema nodosum leprosum (ENL), a reaction in lepromatous leprosy (L‐lep), is a prototypical type III hypersensitivity reaction characterized by immune‐complex deposition and a neutrophilic infiltrate. We investigated the differential gene expression profiles of L‐lep and ENL lesions; both supervised and unsupervised analyses indicated that the different patient groups express a distinct lesional gene profile. The cell adhesion gene cluster, including e‐selectin (E‐sel), was the most overrepresented biological process increased in ENL compared to L‐lep. E‐sel protein was expressed on blood vessels, and was comparatively higher in ENL than L‐lep lesions. IL‐1 and IFN‐γ induced high levels of E‐sel expression on endothelial cells and induced neutrophil adhesion. Thalidomide, an effective treatment for ENL, diminished IL‐1 and IFN‐γ induced E‐sel expression on endothelial cells and diminished neutrophil binding. These data suggest a role for IL‐1 plus IFN‐γ induction of E‐sel on endothelial cells in mediating neutrophil recruitment in the pathogenesis of ENL and type III hypersensitivity reactions.