Dr Weiming Ouyang, Senior Research Fellow, US Food and Drug Administration, US.
A functional adaptive immune system is dependent on a diverse and self-tolerant population of T cells. Our laboratory is interested in understanding the potential role of evolutionally conserved signaling pathways in controlling T cell homeostasis and tolerance. My studies were focused on TGF-ß and Akt-Foxo signaling pathways. By using genetically manipulated mouse models, we reveal that (1) TGF-ß signaling is critical for generation and maintenance of a diverse T cell population, an unexpected function of TGF-ß signaling in addition to its role in controlling T cell tolerance; (2) the family of Foxo transcription factors is essential for T cells to acquire competence during development; (3) the family of Foxo transcription factors controls T cell tolerance by promoting Foxp3 expression during the development of regulatory T (Treg) cells, and establishing the suppressive function of Treg cells. Our studies demonstrate that these ancient signaling pathways are co-opted to regulate T cell homeostasis and tolerance during evolution.