AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the FOXO3-FOXP3 Axis

Juliane Becher, Luca Simula, Claudio Procaccini, Claudia La Rocca, Pasquale D'Acunzo, Valentina Cianfanelli, Vincenzo Gigantino, Gerardo Botti, Francesca Ruffini, Paola Braghetta, Martina Chrisam, Paolo Bonaldo

Research output: Contribution to journalArticle

Abstract

Regulatory T cells (T-reg) are necessary to maintain immunological tolerance and are key players in the control of autoimmune disease susceptibility. Expression of the transcription factor FOXP3 is essential for differentiation of T-reg cells and indispensable for their suppressive function. However, there is still a lack of knowledge about the mechanisms underlying its regulation. Here, we demonstrate that pro-autophagy protein AMBRA1 is also a key modulator of T cells, regulating the complex network that leads to human T-reg differentiation and maintenance. Indeed, through its ability to interact with the phosphatase PP2A, AMBRA1 promotes the stability of the transcriptional activator FOXO3, which, in turn, triggers FOXP3 transcription. Furthermore, we found that AMBRA1 plays a significant role in vivo by regulating T-reg cell induction in mouse models of both tumor growth and multiple sclerosis, thus highlighting the role of AMBRA1 in the control of immune homeostasis.
Original languageUndefined/Unknown
Pages (from-to)592+
JournalDevelopmental Cell
Volume47
Issue number5
DOIs
Publication statusPublished - Dec 3 2018

Cite this

Becher, J., Simula, L., Procaccini, C., La Rocca, C., D'Acunzo, P., Cianfanelli, V., Gigantino, V., Botti, G., Ruffini, F., Braghetta, P., Chrisam, M., & Bonaldo, P. (2018). AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the FOXO3-FOXP3 Axis. Developmental Cell, 47(5), 592+. https://doi.org/10.1016/j.devcel.2018.11.010