Mononuclear cell composition and activation in blood and mucosal tissue of eosinophilic esophagitis

作者：Eva Gruden, Melanie Kienzl, Dušica Ristić, Oliver Kindler, David Markus Kaspret, Sophie Theresa Schmid, Julia Kargl, Eva M. Sturm, Alfred D. Doyle, Benjamin L. Wright, Franziska Baumann‐Durchschein, Julia Konrad, Andreas Blesl, Hansjörg Schlager, Rudolf Schicho · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1347259 · 被引用次数：7 · 研究领域：Eosinophilic Esophagitis、IL-33, ST2, and ILC Pathways、Asthma and respiratory diseases

Introduction Eosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4 + T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing. Methods In this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus. Results Our results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4 + T cells and on myeloid cells in ...