Eosinophils Mediate Tissue Injury in the Autoimmune Skin Disease Bullous Pemphigoid

Abstract

Eosinophils are typically associated with unique inflammatory settings, including allergic inflammation and helminth infections. However, new information suggests that eosinophils contribute more broadly to inflammatory responses and participate in local immune regulation and the tissue remodeling/repair events linked with a variety of diseases. Eosinophilic infiltration has long been a histologic hallmark of bullous pemphigoid (BP), a subepidermal autoimmune blistering disease characterized by autoantibodies directed against basement membrane protein BP180. However, the exact role of eosinophils in disease pathogenesis remains largely unknown. We show here that eosinophils are necessary for IgE autoantibody-mediated BP blister formation in a humanized IgE receptor mouse model of BP. Disease severity is IgE dose dependent and correlates with the degree of eosinophil infiltration in the skin. Furthermore, IgE autoantibodies fail to induce BP in eosinophil-deficient mice, confirming that eosinophils are required for IgE-mediated tissue injury. Thus, eosinophils provide the cellular link between IgE autoantibodies and skin blistering in this murine model of BP. These findings suggest a role for eosinophils in autoimmune disease and have important implications for the treatment of BP and other antibody-mediated inflammatory and autoimmune diseases.

From bench to bedside: evolving therapeutic targets in autoimmune blistering disease

“…Murine models expressing humanized FcεRI and NC16a, the major epitope in BP180, identified IgE‐mediated tissue destruction proceeds through eosinophil activation. Disease severity in this model correlated with IgE levels and identified eosinophils as the major IgE activated effector cells necessary for blister formation . The significance of IgE autoantibodies in BP however remains controversial as they are not universally detected and are not associated with a specific BP phenotype .…”

“…Increased expression of eotaxin‐1 in lesional skin and a serum to lesional gradient in BP patients drives eosinophil infiltration and explains the high concentrations in cellular infiltrates . Eosinophils have a clear pathogenic role in BP . As such, inhibition of its chemotactic signals provides a promising avenue for therapeutic benefit.…”

Role of BP230 autoantibodies in bullous pemphigoid

“…However, the pathogenicity of BP230 IgE has not been studied. The pathogenic role of anti‐BP230 IgE may be elucidated by injection of anti‐BP230 IgE into the humanized IgE receptor eosinophil model as suggested for anti‐hNC16A IgE‐induced BP in the future …”

Treatment of refractory bullous pemphigoid with IFN‐α‐2b: A case report

“…Previous studies have reported the relevance of eosinophils in the pathogenesis of BP. Increasing evidence has been presented on the pathogenic role of eosinophils in BP in mediating tissue damage (Lin et al, ; Moriuchi, Nishie, Ujiie, Natsuga, & Shimizu, ). It was considered that eosinophils, the major actors in the pathogenesis of BP, would inspire novel perspectives for a targeted therapy (Simon, Borradori, & Simon, ).…”