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Publication : Unaltered negative selection and Treg development of self-reactive thymocytes in TCR transgenic Fyn-deficient mice.

First Author  Mamchak AA Year  2010
Journal  Eur J Immunol Volume  40
Issue  2 Pages  539-47
PubMed ID  19904769 Mgi Jnum  J:157790
Mgi Id  MGI:4436973 Doi  10.1002/eji.200939645
Citation  Mamchak AA, et al. (2010) Unaltered negative selection and Treg development of self-reactive thymocytes in TCR transgenic Fyn-deficient mice. Eur J Immunol 40(2):539-47
abstractText  The tyrosine kinase Fyn has been implicated as playing an important role in the generation of both stimulatory and inhibitory signaling events induced by TCR engagement. To assess the role of Fyn for antigen-driven negative selection and Treg development, which are both dependent on the strength and nature of TCR signaling, we generated mice that co-express the transgenes for OVA and the OT-II TCR, which recognizes a peptide from OVA. In mice expressing both transgenes, negative selection, Treg development in the thymus, and the number of Treg in the periphery were each unaffected by ablation of Fyn. Moreover, fyn(-/-) Treg were functional, as assessed in vitro. We further tested the role of Fyn for the adaptor function of c-Cbl, using mice containing a point mutation in c-Cbl that abolishes its E3 ubiquitin ligase function but maintains its adaptor function. The functional and signaling properties of this mutant c-Cbl were unaltered in fyn(-/-) thymocytes. Combined, these data indicate that Fyn was not required for the induction of central tolerance by negative selection, the adaptor protein role of c-Cbl, or the normal development and function of Treg.
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