The serine/threonine protein phosphatase 2A controls autoimmunity.

Autor: Sharabi A; Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: asharabi@bidmc.harvard.edu., Kasper IR; Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States., Tsokos GC; Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
Jazyk: angličtina
Zdroj: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2018 Jan; Vol. 186, pp. 38-42. Date of Electronic Publication: 2017 Jul 21.
DOI: 10.1016/j.clim.2017.07.012
Abstrakt: Protein phosphatase 2A (PP2A) is the first serine/threonine phosphatase recognized to contribute to human and murine lupus immunopathology. PP2A expression in SLE is controlled both epigenetically and genetically, and it is increased in patients with SLE, which contributes to decreased IL-2 production, decreased CD3ζ and increased FcRγ expression on the surface of T cells, increased CREMα expression, hypomethylation of genes associated with SLE pathogenesis, and increased IL-17 production. β regulatory subunit of PP2A regulates IL-2 deprivation-induced T cell death and is decreased in SLE patients. A mouse overexpressing PP2A c in T cells displays peripheral granulocytosis, elevated IL-17 production, and develops glomerulonephritis when challenged. A mouse which lacks PP2A c only in regulatory T cells develops severe autoimmunity and multiorgan inflammation because of loss of restraint on mTORC1 and inability of Foxp3+ cells to regulate conventional T cells. Targeting PP2A in T cell subsets may be therapeutic for SLE and other autoimmune diseases.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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