title: Role of macrophage migration inhibitory factor in the Th2 immune response to epicutaneous sensitization.
abstract: We examined the role of macrophage migration inhibitory factor (MIF) in the generation of the Th2 response using MIF-deficient mice in a model of epicutaneous sensitization to ovalbumin. Lymph node cells from sensitized MIF-deficient mice produce lower levels of Th2 cytokines after antigen challenge when compared to their wild-type counterparts. Sensitized mice lacking MIF show less pulmonary inflammation after intranasal antigen exposure. Mice deficient in CD74, the MIF receptor, also are unable to generate an inflammatory response to epicutaneous sensitization. Examination of the elicitation phase of the atopic response using DO11.10 OVA TCR transgenic animals shows that T cell proliferation and IL-2 production are strongly impaired in MIF-deficient T cells. This defect is most profound when both T cells and antigen-presenting cells are lacking MIF. These data suggest that MIF is crucial both for the sensitization and the elicitation phases of a Th2-type immune response in allergic disease.
authors.affiliation: Department of Medicine, Yale University School of Medicine, The Anlyan Center Room S525, New Haven, CT 06520-8031, USA.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Das
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Moss
authors.forename: Eve
authors.initials: E
authors.lastname: Robinson
authors.forename: Scott
authors.initials: S
authors.lastname: Roberts
authors.forename: Rebecca
authors.initials: R
authors.lastname: Levy
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mizue
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.forename: Courtney
authors.initials: C
authors.lastname: McDonald
authors.forename: Robert E
authors.initials: RE
authors.lastname: Tigelaar
authors.forename: Christina A
authors.initials: CA
authors.lastname: Herrick
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
mesh_terms: D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000938:Antigen-Presenting Cells / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006969:Hypersensitivity, Immediate; D007114:Immunization; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D017252:CD3 Complex; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008263:Macrophage Migration-Inhibitory Factors; C045084:invariant chain; D010047:Ovalbumin; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse