Affiliation:
1. Department of Immunobiology, Yale University School of Medicine, New Haven, CT 1
2. Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea 2
3. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 3
Abstract
IgE mediates allergic responses by coating mast cell or basophil surfaces and inducing degranulation upon binding a specific allergen. IgE can also be spontaneously produced in the absence of foreign allergens; yet the origin, regulation, and functions of such “natural” IgE still remain largely unknown. Here, we find that glucocorticoids enhance the production of IgE in B cells both in vivo and ex vivo without antigenic challenge. Such IgE production is promoted by B cell–intrinsic glucocorticoid receptor signaling that reinforces CD40 signaling and synergizes with the IL-4/STAT6 pathway. In addition, we found that rare B cells in the mesenteric lymph nodes are responsible for the production of glucocorticoid-inducible IgE. Furthermore, locally produced glucocorticoids in the gut may induce natural IgE during perturbations of gut homeostasis, such as dysbiosis. Notably, mice preemptively treated with glucocorticoids were protected from subsequent pathogenic anaphylaxis. Together, our results suggest that glucocorticoids, classically considered to be broadly immunosuppressive, have a selective immunostimulatory role in B cells.
Funder
Howard Hughes Medical Institute
Blavatnik Family Foundation
Food Allergy Science Initiative
National Institutes of Health
Yonsei Research Fund
Yonsei Signature Research Cluster Program of 2022
National Research Foundation of Korea, Ministry of Science, ICT and Future Planning
International Human Frontier Science Program Organization
Jane Coffin Childs Memorial Fund for Medical Research
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
5 articles.
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