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CARMA1 is critical for the development of allergic airway inflammation in a murine model of asthma.

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.

Pubmed ID: 16751370

Authors

  • Medoff BD
  • Seed B
  • Jackobek R
  • Zora J
  • Yang Y
  • Luster AD
  • Xavier R

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

June 15, 2006

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI27849
  • Agency: NIAID NIH HHS, Id: AI46731
  • Agency: NIDDK NIH HHS, Id: DK43351
  • Agency: NHLBI NIH HHS, Id: K08 HL072775
  • Agency: NHLBI NIH HHS, Id: K08 HL072775
  • Agency: NIDDK NIH HHS, Id: P30 DK040561
  • Agency: NIDDK NIH HHS, Id: P30 DK040561-11
  • Agency: NHLBI NIH HHS, Id: R01 HL088297

Mesh Terms

  • Adoptive Transfer
  • Allergens
  • Animals
  • Apoptosis Regulatory Proteins
  • Asthma
  • Bronchial Hyperreactivity
  • CARD Signaling Adaptor Proteins
  • Cytokines
  • Disease Models, Animal
  • Guanylate Kinase
  • Immunoglobulin E
  • Immunophenotyping
  • Lung
  • Lymph Nodes
  • Lymphocyte Activation
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin
  • Respiratory Hypersensitivity
  • Th2 Cells