title: IL-4 Haploinsufficiency Specifically Impairs IgE Responses against Allergens in Mice.
abstract: Polymorphisms in genes involved in IL-4 responses segregate with allergic disease risk and correlate with IgE levels in humans, and IL-4 promotes IgE and IgG1 Ab production against allergens in mice. We report that mice with only one intactIl4gene copy are significantly impaired in their ability to make specific IgE responses against allergens, whereas IgG1 responses to allergens remain unaffected.Il4-hemizygosity also resulted in a modest but detectable drop in IL-4 production by CD4+T cells isolated from lymph nodes and prevented IgE-dependent oral allergen-induced diarrhea. We conclude that a state of haploinsufficiency for theIl4gene locus is specifically relevant for IL-4-dependent IgE responses to allergens with the amount of IL-4 produced in the hemizygous condition falling close to the threshold required for switching to IgE production. These results may be relevant for how polymorphisms in genes affecting IL-4 responses influence the risk of IgE-mediated allergic disease in humans.
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand.|Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143.|Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Robinson
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
authors.forename: Melanie
authors.initials: M
authors.lastname: Prout
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
authors.forename: Helen
authors.initials: H
authors.lastname: Mearns
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
authors.forename: Ryan
authors.initials: R
authors.lastname: Kyle
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
authors.forename: Mali
authors.initials: M
authors.lastname: Camberis
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Forbes-Blom
authors.affiliation: Laboratories of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143.|Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143.|Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Christopher D C
authors.identifier: 0000-0002-1879-9047
authors.initials: CD
authors.lastname: Allen
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand; glegros@malaghan.org.nz.
authors.forename: Graham
authors.identifier: 0000-0002-5721-0442
authors.initials: G
authors.lastname: Le Gros
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D057895:Haploinsufficiency; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D051379:Mice; D011058:Pollen / Q000276:immunology; D011110:Polymorphism, Genetic
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E