Commensal bacteria–derived signals regulate basophil hematopoiesis and allergic inflammation
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Open Access
- 25 March 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 18 (4), 538-546
- https://doi.org/10.1038/nm.2657
Abstract
Alterations in commensal bacteria are associated with an increased risk of allergic disease. David Artis and his colleagues now report that commensal-derived signals influence basophil development and TH2 cytokine–dependent allergic airway inflammation by suppressing serum IgE levels. Individuals with hyper IgE syndrome also have elevated circulating basophil numbers, suggesting a mechanistic link between commensal bacteria, B cell–mediated production of IgE and basophil hematopoiesis. Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (TH2) cytokine-dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we find that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted in elevated serum IgE concentrations, increased steady-state circulating basophil populations and exaggerated basophil-mediated TH2 cell responses and allergic inflammation. Elevated serum IgE levels correlated with increased circulating basophil populations in mice and subjects with hyperimmunoglobulinemia E syndrome. Furthermore, B cell–intrinsic expression of myeloid differentiation factor 88 (MyD88) was required to limit serum IgE concentrations and circulating basophil populations in mice. Commensal-derived signals were found to influence basophil development by limiting proliferation of bone marrow–resident precursor populations. Collectively, these results identify a previously unrecognized pathway through which commensal-derived signals influence basophil hematopoiesis and susceptibility to TH2 cytokine–dependent inflammation and allergic disease.Keywords
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