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

BD Medoff, B Seed, R Jackobek, J Zora… - The Journal of …, 2006 - journals.aai.org
BD Medoff, B Seed, R Jackobek, J Zora, Y Yang, AD Luster, R Xavier
The Journal of Immunology, 2006journals.aai.org
CARMA1 has been shown to be important for Ag-stimulated activation of NF-κB 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 …
Abstract
CARMA1 has been shown to be important for Ag-stimulated activation of NF-κB 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-κB for therapy in asthma.
journals.aai.org