Source:http://linkedlifedata.com/resource/pubmed/id/12244137
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
2002-9-23
|
| pubmed:abstractText |
TGF-beta regulation of immune homeostasis has been investigated in the context of cytokine knockout (TGF-beta null) mice, in which particular TGF-beta isoforms are disrupted throughout the entire organism, as well as in B and T cell-specific transgenic models, but to date the immunoregulatory effects of TGF-beta have not been addressed in the context of an in vivo mouse model in which multi-isoform TGF-beta signaling is abrogated in multiple leukocyte lineages while leaving nonhemopoietic tissue unaffected. Here we report the development of a murine model of TGF-beta insensitivity limited to the hemopoietic tissue of adult wild-type C57BL/6 mice based on retroviral-mediated gene transfer of a dominant negative TGF-beta type II receptor targeting murine bone marrow. Unlike the lymphoproliferative syndrome observed in TGF-beta1-deficient mice, the disruption of TGF-beta signaling in bone marrow-derived cells leads to dramatic expansion of myeloid cells, primarily monocytes/macrophages, and is associated with cachexia and mortality in lethally irradiated mice reconstituted with dominant negative receptor-transduced bone marrow. Surprisingly, there was a notable absence of T cell expansion in affected animals despite the observed differentiation of most cells in the T cell compartment to a memory phenotype. These results indicate not only that TGF-beta acts as a negative regulator of immune function, but that lack of functional TGF-beta signaling in the myeloid compartment of adult mice may trigger suppression of lymphocytes, which would otherwise proliferate when rendered insensitive to TGF-beta.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD44,
http://linkedlifedata.com/resource/pubmed/chemical/L-Selectin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/transforming growth factor-beta...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
169
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3485-91
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:12244137-3T3 Cells,
pubmed-meshheading:12244137-Animals,
pubmed-meshheading:12244137-Antigens, CD44,
pubmed-meshheading:12244137-Cachexia,
pubmed-meshheading:12244137-Cell Differentiation,
pubmed-meshheading:12244137-Cell Lineage,
pubmed-meshheading:12244137-Cells, Cultured,
pubmed-meshheading:12244137-Gene Expression Regulation, Viral,
pubmed-meshheading:12244137-Gene Transfer Techniques,
pubmed-meshheading:12244137-Genetic Vectors,
pubmed-meshheading:12244137-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:12244137-Hematopoietic Stem Cells,
pubmed-meshheading:12244137-Immunologic Memory,
pubmed-meshheading:12244137-Immunophenotyping,
pubmed-meshheading:12244137-Inflammation,
pubmed-meshheading:12244137-L-Selectin,
pubmed-meshheading:12244137-Lymphocyte Activation,
pubmed-meshheading:12244137-Mice,
pubmed-meshheading:12244137-Mice, Inbred C57BL,
pubmed-meshheading:12244137-Myeloid Progenitor Cells,
pubmed-meshheading:12244137-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12244137-Radiation Chimera,
pubmed-meshheading:12244137-Receptors, Interleukin-2,
pubmed-meshheading:12244137-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:12244137-Retroviridae,
pubmed-meshheading:12244137-T-Lymphocyte Subsets,
pubmed-meshheading:12244137-Transduction, Genetic,
pubmed-meshheading:12244137-Transgenes
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Reconstitution of lethally irradiated adult mice with dominant negative TGF-beta type II receptor-transduced bone marrow leads to myeloid expansion and inflammatory disease.
|
| pubmed:affiliation |
Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
|