title: CARMA1 is critical for the development of allergic airway inflammation in a murine model of asthma.
abstract: CARMA1 has been shown to be important for Ag-stimulated activation of NF-kappaB in lymphocytes in vitro and thus could be a novel therapeutic target in inflammatory diseases such as asthma. In the present study, we demonstrate that mice with deletion in the CARMA1 gene (CARMA1(-/-)) do not develop inflammation in a murine model of asthma. Compared with wild-type controls, CARMA1(-/-) mice did not develop airway eosinophilia, had no significant T cell recruitment into the airways, and had no evidence for T cell activation in the lung or draining lymph nodes. In addition, the CARMA1(-/-) mice had significantly decreased levels of IL-4, IL-5, and IL-13, did not produce IgE, and did not develop airway hyperresponsiveness or mucus cell hypertrophy. However, adoptive transfer of wild-type Th2 cells into CARMA1(-/-) mice restored eosinophilic airway inflammation, cytokine production, airway hyperresponsiveness, and mucus production. This is the first demonstration of an in vivo role for CARMA1 in a disease process. Furthermore, the data clearly show that CARMA1 is essential for the development of allergic airway inflammation through its role in T lymphocytes, and may provide a novel means to inhibit NF-kappaB for therapy in asthma.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, 02129, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.forename: Brian
authors.initials: B
authors.lastname: Seed
authors.forename: Ryan
authors.initials: R
authors.lastname: Jackobek
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zora
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.forename: Ramnik
authors.initials: R
authors.lastname: Xavier
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D053468:CARD Signaling Adaptor Proteins; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D051528:Guanylate Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D016130:Immunophenotyping; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018418:Th2 Cells / Q000637:transplantation
chemical_list: D000485:Allergens; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; C496467:Card11 protein, mouse; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin; D051528:Guanylate Kinases