Epithelial Barrier Dysfunction in Type 2 Inflammatory Diseases

Abstract

This satellite symposium took place during the 49th annual meeting of the European Society for Dermatological Research (ESDR). Prof Dávila began the symposium by describing the immunology behind Type 2 inflammation as a complex interaction between environmental factors, immune response, and barrier dysfunction. He explained that the principal cells participating in innate Type 2 immunity are Type 2 innate lymphoid cells (ILC2), eosinophils, basophils, and mast cells, and that Th2 lymphocytes, dendritic cells (DC), and their main cytokines (IL-4, IL-5, and IL-13) comprise the adaptive arm of the Type 2 immune response and are essential in IgE-mediated reactions. Prof Seneschal followed by explaining that Type 2 inflammation in atopic dermatitis (AD) is a combination of immune and epidermal barrier components influenced by genetic and environmental factors. Epidermal barrier proteins are expressed in lower levels in AD, and other proteins are also dysregulated, disrupting tight junctions. Both lesional and nonlesional skin in patients with AD show epithelial barrier dysfunction, and inflammation can lead to a vicious cycle of itching and damage. Prof Dahlén concluded the meeting by explaining that airway inflammation is one of the major factors involved in Type 2 asthma, and this can be driven by an allergic route, involving mast cells, or a nonallergic route, involving ILC2. Inflammatory cytokines also increase mucus production, one of the main causes of asthma-related death. Recent studies of asthma immunology have suggested that ILC2 are subject to feedback modulation by prostaglandin D2 (PGD2), and that both IL-4 and IL-13 are involved in hyper-responsiveness in asthmatic lung tissue.