title: Immunoglobulin E plays an immunoregulatory role in lupus.
abstract: The (patho)physiological role of IgE in nonallergic inflammatory diseases is not well understood. Here, we explored the effect of IgE deficiency on the inflammatory response in FcγRIIB-deficient mice as well as in mice carrying both a deletion of FcγRIIB and the chromosomal translocation of Y-linked autoimmune acceleration (Yaa) that hastens and results in a more aggressive lupuslike disease in these mice. The findings show that deficiency of IgE delays disease development and severity as demonstrated by reduced autoantibody production and amelioration of organ pathologies. This was associated with decreased numbers of plasma cells and reduced levels of IgG2b and IgG3. Unexpectedly, the loss of IgE also caused a striking decrease of immune cell infiltration in secondary lymphoid organs with a marked effect on the presence of dendritic cells, monocytes, neutrophils, and eosinophils in these organs and decreased activation of basophils. The presence of autoreactive IgE in human systemic lupus erythematosus subjects was also associated with increased basophil activation and enhanced disease activity. These findings argue that IgE facilitates the amplification of autoimmune inflammation.
authors.affiliation: Molecular Immunology Section, Laboratory of Molecular Immunogenetics, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252 Universite Paris Diderot, Laboratoire d'Excellence Inflamex, DHU FIRE, 75018 Paris, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dema
authors.affiliation: Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252 Universite Paris Diderot, Laboratoire d'Excellence Inflamex, DHU FIRE, 75018 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Charles
authors.affiliation: Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252 Universite Paris Diderot, Laboratoire d'Excellence Inflamex, DHU FIRE, 75018 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pellefigues
authors.affiliation: Molecular Immunology Section, Laboratory of Molecular Immunogenetics, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Tiffany K
authors.initials: TK
authors.lastname: Ricks
authors.affiliation: Molecular Immunology Section, Laboratory of Molecular Immunogenetics, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Molecular Immunology Section, Laboratory of Molecular Immunogenetics, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Molecular Immunology Section, Laboratory of Molecular Immunogenetics, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Jorg
authors.initials: J
authors.lastname: Scheffel
authors.affiliation: Molecular Immunology Section, Laboratory of Molecular Immunogenetics, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Hasni
authors.affiliation: Diagnostic and Research Services Branch, Office of the Director, Autoimmunity and Functional Genomics Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Victoria
authors.initials: V
authors.lastname: Hoffman
authors.affiliation: Department of Nephrology, Department of Internal Medicine, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Faculte de Medecine site Bichat, 75018 Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Jablonski
authors.affiliation: Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252 Universite Paris Diderot, Laboratoire d'Excellence Inflamex, DHU FIRE, 75018 Paris, France Department of Nephrology, Department of Internal Medicine, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Faculte de Medecine site Bichat, 75018 Paris, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Sacré
authors.affiliation: Department of Nephrology, Department of Internal Medicine, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Faculte de Medecine site Bichat, 75018 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Gobert
authors.affiliation: Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252 Universite Paris Diderot, Laboratoire d'Excellence Inflamex, DHU FIRE, 75018 Paris, France Department of Nephrology, Department of Internal Medicine, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Faculte de Medecine site Bichat, 75018 Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Papo
authors.affiliation: Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252 Universite Paris Diderot, Laboratoire d'Excellence Inflamex, DHU FIRE, 75018 Paris, France Department of Nephrology, Department of Internal Medicine, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Faculte de Medecine site Bichat, 75018 Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Daugas
authors.affiliation: Diagnostic and Research Services Branch, Office of the Director, Autoimmunity and Functional Genomics Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Steve
authors.initials: S
authors.lastname: Crampton
authors.affiliation: Diagnostic and Research Services Branch, Office of the Director, Autoimmunity and Functional Genomics Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolland
authors.affiliation: Molecular Immunology Section, Laboratory of Molecular Immunogenetics, Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 juan_rivera@nih.gov.
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D016516:CD4-CD8 Ratio; D016022:Case-Control Studies; D004195:Disease Models, Animal; D006801:Humans; D007073:Immunoglobulin E / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D056747:Immunomodulation; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics
chemical_list: D001323:Autoantibodies; D017452:Receptors, IgG; D007073:Immunoglobulin E