Article

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

Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, 02129, USA.
The Journal of Immunology (impact factor: 5.79). 07/2006; 176(12):7272-7. pp.7272-7
Source: PubMed

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.

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Keywords

Ag-stimulated activation
 
airway eosinophilia
 
airway hyperresponsiveness
 
allergic airway inflammation
 
CARMA1 gene
 
cytokine production
 
disease process
 
draining lymph nodes
 
eosinophilic airway inflammation
 
first demonstration
 
IgE
 
IL-4
 
inflammatory diseases
 
lymphocytes
 
mucus cell hypertrophy
 
murine model
 
novel therapeutic target
 
significant T cell recruitment
 
T lymphocytes
 
wild-type Th2 cells