![]() While IgE-mediated inflammatory effector responses, such as extravasation, mucus secretion, and gut peristalsis, are considered protective against helminths and noxious chemicals, they can also be pathological if misdirected or excessive ( Anthony et al., 2007 Palm et al., 2012). In the initial presence of allergen and T cell signals, allergen-specific B cells undergo class switch recombination and somatic hypermutation (SHM) to produce high-affinity IgE, which coats the high-affinity Fc epsilon receptor I (FcεRI) expressed on surfaces of innate immune sentinels like mast cells and basophils ( He et al., 2015 Oettgen, 2016 Stavnezer and Schrader, 2014). Type 2 immunity is mediated primarily by T helper 2 cells alongside B cells that secrete IgE and IgG1 antibodies ( Lloyd and Snelgrove, 2018 Palm et al., 2012). Unlike type 1 immunity, which deals with pathogens such as bacteria and viruses, type 2 immunity defends the body from macroparasites, noxious chemicals, and toxins ( Iwasaki and Medzhitov, 2015 Palm et al., 2012). Together, our results suggest that glucocorticoids, classically considered to be broadly immunosuppressive, have a selective immunostimulatory role in B cells.Īllergy, a leading chronic condition affecting hundreds of millions of people worldwide, targets diverse and seemingly innocuous environmental stimuli such as pollen or peanut by activating type 2 immune responses ( Lloyd and Snelgrove, 2018 Palm et al., 2012). Notably, mice preemptively treated with glucocorticoids were protected from subsequent pathogenic anaphylaxis. Furthermore, locally produced glucocorticoids in the gut may induce natural IgE during perturbations of gut homeostasis, such as dysbiosis. In addition, we found that rare B cells in the mesenteric lymph nodes are responsible for the production of glucocorticoid-inducible IgE. Such IgE production is promoted by B cell–intrinsic glucocorticoid receptor signaling that reinforces CD40 signaling and synergizes with the IL-4/STAT6 pathway. Here, we find that glucocorticoids enhance the production of IgE in B cells both in vivo and ex vivo without antigenic challenge. ![]() 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. ![]() IgE mediates allergic responses by coating mast cell or basophil surfaces and inducing degranulation upon binding a specific allergen.
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