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Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-β
Yang X.4; Letterio J.J.1; Lechleider R.J.1; Chen L.4; Hayman R.3; Gu H.3; Roberts A.B.1; Deng C.4
1999-03-01
Source PublicationEMBO Journal
ISSN02614189
Volume18Issue:5Pages:1280-1291
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.

KeywordBacterial Infections Gene Targeting Inflammation Smad3 Tgf-β Signaling
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000079184600018
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Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.National Cancer Institute
2.Beijing Institute of Biotechnology
3.National Institute of Allergy and Infectious Diseases
4.National Institute of Diabetes and Digestive and Kidney Diseases
Recommended Citation
GB/T 7714
Yang X.,Letterio J.J.,Lechleider R.J.,et al. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-β[J]. EMBO Journal,1999,18(5):1280-1291.
APA Yang X..,Letterio J.J..,Lechleider R.J..,Chen L..,Hayman R..,...&Deng C..(1999).Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-β.EMBO Journal,18(5),1280-1291.
MLA Yang X.,et al."Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-β".EMBO Journal 18.5(1999):1280-1291.
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