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T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation.

Immunity | May 24, 2007

http://www.ncbi.nlm.nih.gov/pubmed/17481928

TGF-beta1 is a regulatory cytokine with a pleiotropic role in immune responses. TGF-beta1 is widely expressed in leukocytes and stromal cells. However, the functions of TGF-beta1 expressed by specific lineages of cells remain unknown in vivo. Here, we show that mice with a T cell-specific deletion of the Tgfb1 gene developed lethal immunopathology in multiple organs, and this development was associated with enhanced T cell proliferation, activation, and CD4+ T cell differentiation into T helper 1 (Th1) and Th2 cells. TGF-beta1 produced by Foxp3-expressing regulatory T cells was required to inhibit Th1-cell differentiation and inflammatory-bowel disease in a transfer model. In addition, T cell-produced TGF-beta1 promoted Th17-cell differentiation and was indispensable for the induction of experimental autoimmune encephalomyelitis. These findings reveal essential roles for T cell-produced TGF-beta1 in controlling differentiation of T helper cells and controlling inflammatory diseases.

Pubmed ID: 17481928 RIS Download

Mesh terms: Animals | Cell Differentiation | Cells, Cultured | Colitis | Encephalomyelitis, Autoimmune, Experimental | Forkhead Transcription Factors | Gene Deletion | Gene Expression Regulation | Homeostasis | Immune Tolerance | Lymphocyte Activation | Mice | Mice, Knockout | T-Lymphocytes | Transforming Growth Factor beta1

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Associated grants

  • Agency: NIAMS NIH HHS, Id: R01 AR060723
  • Agency: NIDDK NIH HHS, Id: R01DK51665

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