Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites

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Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites

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Title: Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites
Author: Platzer, Barbara; Baker, Kristi; Vera, Miguel Pinilla; Singer, Kathleen; Panduro, Marisella; Lexmond, Willem S.; Turner, Devin; Vargas, Sara O.; Kinet, Jean-Pierre; Maurer, Dieter; Baron, Rebecca M.; Blumberg, Richard S.; Fiebiger, Edda

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Citation: Platzer, B., K. Baker, M. P. Vera, K. Singer, M. Panduro, W. S. Lexmond, D. Turner, et al. 2014. “Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites.” Mucosal immunology 8 (3): 516-532. doi:10.1038/mi.2014.85. http://dx.doi.org/10.1038/mi.2014.85.
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Abstract: Antigen-mediated crosslinking of Immunoglobulin E (IgE) bound to mast cells/basophils via FcεRI, the high affinity IgE Fc-receptor, is a well-known trigger of allergy. In humans, but not mice, dendritic cells (DCs) also express FcεRI that is constitutively occupied with IgE. In contrast to mast cells/basophils, the consequences of IgE/FcεRI signals for DC function remain poorly understood. We show that humanized mice that express FcεRI on DCs carry IgE like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/FcεRI crosslinking fails to induce maturation or production of inflammatory mediators in human DCs and FcεRI-humanized DCs. Furthermore, conferring expression of FcεRI to DCs decreases the severity of food allergy and asthma in disease-relevant models suggesting anti-inflammatory IgE/FcεRI signals. Consistent with the improved clinical parameters in vivo, antigen-specific IgE/FcεRI crosslinking on papain or LPS-stimulated DCs inhibits the production of pro-inflammatory cytokines and chemokines. Migration assays confirm that the IgE-dependent decrease in cytokine production results in diminished recruitment of mast cell progenitors; providing a mechanistic explanation for the reduced mast cell-dependent allergic phenotype observed in FcεRI-humanized mice. Our study demonstrates a novel immune regulatory function of IgE and proposes that DC-intrinsic IgE signals serve as a feedback mechanism to restrain allergic tissue inflammation.
Published Version: doi:10.1038/mi.2014.85
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363306/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845147
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