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Graduate and Postdoctoral Research Symposium 2020 has ended
avatar for Juliano Tiburcio de Freitas

Juliano Tiburcio de Freitas

The Role of Notch1 in Regulatory T Cell Function
PosterPresenter #22
Postdoctoral Associate in Dermatology
Notch is a conserved signaling pathway that, among many functions, regulates the development and function of the immune system. The critical role of Notch during T cell lineage commitment and maturation has long been established. Tregs are a small population of CD4+ Helper T cells that have strong immunosuppressive abilities. The differentiation, expansion, and maintenance of Treg functions rely on Notch signaling, however, the functions of different Notch receptors in Tregs are poorly understood. Our data show that naïve Tregs express Notch1, 2 and 4 but not Notch3. To further understand the role of Notch receptors in Tregs function, we made use of both a Notch1 specific neutralizing antibody (anti-N1) we have developed, as well as dibenzazepine (DBZ), a ɣ-secretase inhibitor which is able to inhibit all Notch receptors. Treatment of Tregs with the anti-N1 antibody lead to reduced Tregs associated markers (FOXP3, CTLA-4, IL-10, TGF-β), in both un-stimulated and Jagged-1 stimulated cells. Our results suggest that Tregs are sensitive to anti-N1 and Notch1 is required for Treg function. Interestingly, Tregs might populate tumors and suppress anti-tumor immunity. Notch 2, but not Notch1, has been shown to be required for cytotoxic lymphocytes anti-tumor features. Therefore, anti-N1 treatment might improve the outcome of immunotherapies regimens. We are currently addressing the therapeutic efficacy of anti-N1 in melanoma models in conjunction with immunocheckpoint inhibitors.