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Abrogation of TGFβ Signaling in T Cells Leads to Spontaneous T Cell Differentiation and Autoimmune Disease
Open accessAbstract
Targeted mutation of TGFbeta1 in mice demonstrated that TGFbeta1 is one of the key negative regulators of immune homeostasis, as its absence leads to activation of a self-targeted immune response. Nevertheless, because of the highly pleiotropic properties of TGFbeta and the presence of TGFbeta receptors on most cell types, its biologic role in the regulation of immune homeostasis is not yet understood. To limit the consequences of TGFbeta effects to a single cell type, we developed a transgenic approach to abrogate the TGFbeta response in key immune cells. Specifically, we expressed a dominant-negative TGFbeta receptor type II under a T cell-specific promoter and created a mouse model where signaling by TGFbeta is blocked specifically in T cells. Using this transgenic model, we show that T cell homeostasis requires TGFbeta signaling in T cells.
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Kulkarni, A. B., Huh, C. G., Becker, D., Geiser, A., Lyght, M., Flanders, K. C., Roberts, A. B., Sporn, M. B., Ward, J. M., & Karlsson, S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.770 · Cited by 1,967
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Quintana, F. J., Basso, A. S., Iglesias, A. H., Korn, T., Farez, M. F., Bettelli, E., Caccamo, M., Oukka, M., & Weiner, H. L. (2008) · Nature · doi:10.1038/nature06880 · Cited by 1,865
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Tauriello, D. V. F., Palomo-Ponce, S., Stork, D., Berenguer-Llergo, A., Badia-Ramentol, J., Iglesias, M., Sevillano, M., Ibiza, S., Cañellas, A., Hernando-Momblona, X., et al. (2018) · Nature · doi:10.1038/nature25492 · Cited by 1,851
Metadata
- Authors
- Gorelik, L., & Flavell, R. A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 12
- Issue
- 2
- Pages
- 171-181
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2039347592
- Cited by
- 962
- References
- 1
- FWCI
- 14.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Gorelik, L., & Flavell, R. A. (2000). Abrogation of TGFβ Signaling in T Cells Leads to Spontaneous T Cell Differentiation and Autoimmune Disease. Immunity. https://doi.org/10.1016/s1074-7613(00)80170-3
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
