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- Title
Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-ß.
- Authors
Xiao Yang; Letterio, John J.; Lechleider, Robert J.; Lin Chen; Huyman, Russ; Hua Gu; Roberts, Anita B.; Chuxia Deng
- Abstract
SMAD3 is one of the intracellular mediators that transduces signals from transforming growth factor-β (TGF-β) and activin receptors. We show that SMAD3 mutant mice generated by gene targeting die between 1 and 8 months due to a primary defect in immune function. Symptomatic mice exhibit thymic involution, enlarged lymph nodes, and formation of bacterial abscesses adjacent to mucosal surfaces. Mutant T cells exhibit an activated phenotype in vivo, and are not inhibited by TGF-β1 in vitro. Mutant neutrophils are also impaired in their chemotactic response toward TGF-β. Chronic intestinal inflammation is infrequently associated with colonic adenocarcinoma in mice older than 6 months of age. These data suggest that SMAD3 has an important role in TGF-β-mediated regulation of T cell activation and mucosal immunity, and that the loss of these functions is responsible for chronic infection and the lethality of Smad3-null mice.
- Publication
EMBO Journal, 1999, Vol 18, Issue 5, p1280
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/18.5.1280