| Literature DB >> 30513302 |
Juliane Becher1, Luca Simula2, Elisabetta Volpe1, Claudio Procaccini3, Claudia La Rocca4, Pasquale D'Acunzo2, Valentina Cianfanelli5, Flavie Strappazzon6, Ignazio Caruana2, Francesca Nazio2, Gerrit Weber2, Vincenzo Gigantino7, Gerardo Botti7, Fabiola Ciccosanti8, Giovanna Borsellino1, Silvia Campello6, Georgia Mandolesi1, Marco De Bardi1, Gian Maria Fimia9, Marcello D'Amelio10, Francesca Ruffini11, Roberto Furlan11, Diego Centonze12, Gianvito Martino11, Paola Braghetta13, Martina Chrisam13, Paolo Bonaldo14, Giuseppe Matarese15, Franco Locatelli16, Luca Battistini1, Francesco Cecconi17.
Abstract
Regulatory T cells (Treg) 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 Treg 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 Treg 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 Treg cell induction in mouse models of both tumor growth and multiple sclerosis, thus highlighting the role of AMBRA1 in the control of immune homeostasis.Entities:
Keywords: PP2A; autophagy; experimental autoimmune encephalomyelitis; immune surveillance; multiple sclerosis; regulatory T cell
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Year: 2018 PMID： 30513302 DOI： 10.1016/j.devcel.2018.11.010
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270