Phosphatase PP2A is requisite for the function of regulatory T cells

Autor: George C. Tsokos, Abel Suárez-Fueyo, Noé Rodríguez-Rodríguez, Sokratis A. Apostolidis, José C. Crispín, Maria Tsokos, Nikolina Dioufa, Esra Ozcan
Rok vydání: 2015
Předmět:
0301 basic medicine
Male
Immunoproliferative disorder
Immunology
Immunoblotting
chemical and pharmacologic phenomena
Autoimmunity
Mice
Transgenic
macromolecular substances
mTORC1
Biology
Mechanistic Target of Rapamycin Complex 1
medicine.disease_cause
Ceramides
Jurkat cells
T-Lymphocytes
Regulatory
Autoimmune Diseases
03 medical and health sciences
Jurkat Cells
Immune system
immune system diseases
hemic and lymphatic diseases
medicine
Immunology and Allergy
Animals
Humans
Protein Phosphatase 2
Phosphorylation
PI3K/AKT/mTOR pathway
Cells
Cultured
Autoimmune disease
Mice
Knockout
TOR Serine-Threonine Kinases
Peripheral tolerance
hemic and immune systems
medicine.disease
Flow Cytometry
Lymphoproliferative Disorders
3. Good health
Cell biology
Mice
Inbred C57BL
030104 developmental biology
Multiprotein Complexes
Female
Signal Transduction
Zdroj: Nature immunology. 17(5)
ISSN: 1529-2916
Popis: Homeostasis of the immune system depends on the proper function of regulatory T cells (T(reg) cells). Compromised suppressive activity of T(reg) cells leads to autoimmune disease and graft rejection and promotes anti-tumor immunity. Here we report a previously unrecognized requirement for the serine-threonine phosphatase PP2A in the function of T(reg) cells. T(reg) cells exhibited high PP2A activity, and T(reg) cell-specific ablation of the PP2A complex resulted in a severe, multi-organ, lymphoproliferative autoimmune disorder. Mass spectrometry revealed that PP2A associated with components of the mTOR metabolic-checkpoint kinase pathway and suppressed the activity of the mTORC1 complex. In the absence of PP2A, T(reg) cells altered their metabolic and cytokine profile and were unable to suppress effector immune responses. Therefore, PP2A is required for the function of T(reg) cells and the prevention of autoimmunity.
Databáze: OpenAIRE
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