| First Author | Medoff BD | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 12 | Pages | 7272-7 |
| PubMed ID | 16751370 | Mgi Jnum | J:132226 |
| Mgi Id | MGI:3775540 | Doi | 10.4049/jimmunol.176.12.7272 |
| Citation | Medoff BD, et al. (2006) CARMA1 is critical for the development of allergic airway inflammation in a murine model of asthma. J Immunol 176(12):7272-7 |
| abstractText | 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. |
