Protein phosphatase 2A is requisite for the function of regulatory T cells
Apostolidis, Sokratis A.
Crispín, José C.
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CitationApostolidis, Sokratis A., Noé Rodríguez-Rodríguez, Abel Suárez-Fueyo, Nikolina Dioufa, Esra Ozcan, José C. Crispín, Maria G. Tsokos, and George C. Tsokos. 2015. “Protein phosphatase 2A is requisite for the function of regulatory T cells.” Nature immunology 17 (5): 556-564. doi:10.1038/ni.3390. http://dx.doi.org/10.1038/ni.3390.
AbstractImmune homeostasis depends on the proper function of regulatory T (Treg) cells. Compromised Treg cell suppressive activity leads to autoimmune disease, graft rejection and promotes anti-tumor immunity. Here we report the previously unrecognized requirement of the serine/threonine phosphatase Protein Phosphatase 2A (PP2A) for the function of Treg cells. Treg cells exhibited high PP2A activity and Treg cell-specific ablation of the PP2A complex resulted in a severe, multi-organ, lymphoproliferative autoimmune disorder. Mass spectrometric analysis revealed that PP2A associates with components of the mTOR pathway and suppresses mTORC1 activity. In the absence of PP2A, Treg cells altered their metabolic and cytokine profile and were unable to suppress effector immune responses. Therefore, PP2A is requisite for the function of Treg cells and the prevention of autoimmunity.
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