Role of Macrophage Migration Inhibitory Factor in the Th2 Immune Response to Epicutaneous Sensitization

• Published in: Journal of clinical immunology Vol. 31; no. 4; pp. 666 - 680
• Main Authors: Das, Rituparna, Moss, Jeremy E., Robinson, Eve, Roberts, Scott, Levy, Rebecca, Mizue, Yuka, Leng, Lin, McDonald, Courtney, Tigelaar, Robert E., Herrick, Christina A., Bucala, Richard
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-08-2011; Springer Nature B.V
• Subjects: Administration, Cutaneous; Administration, Intranasal; Animals; Antibodies, Monoclonal - administration & dosage; Antigen-Presenting Cells - immunology; Antigens, Differentiation, B-Lymphocyte - genetics; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Differentiation, B-Lymphocyte - metabolism; Biomedical and Life Sciences; Biomedicine; Bone Marrow Cells; CD3 Complex - immunology; Cell Proliferation; Cytokines - biosynthesis; Cytokines - immunology; Female; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Hypersensitivity, Immediate; Immunization; Immunology; Infectious Diseases; Interleukin-2 - biosynthesis; Interleukin-2 - immunology; Internal Medicine; Intramolecular Oxidoreductases - deficiency; Intramolecular Oxidoreductases - genetics; Intramolecular Oxidoreductases - immunology; Lung - immunology; Lung - pathology; Lymph Nodes - immunology; Macrophage Migration-Inhibitory Factors - deficiency; Macrophage Migration-Inhibitory Factors - genetics; Macrophage Migration-Inhibitory Factors - immunology; Macrophages; Medical Microbiology; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin - administration & dosage; Ovalbumin - immunology; Pneumonia - immunology; Pneumonia - pathology; Th2 Cells - immunology; macrophage migration inhibitory factor; Th2 response; Atopic inflammation
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-011-9541-7

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.