دورية أكاديمية
The PP2A regulatory subunit PPP2R2A controls NAD + biosynthesis to regulate T cell subset differentiation in systemic autoimmunity.
| العنوان: | The PP2A regulatory subunit PPP2R2A controls NAD + biosynthesis to regulate T cell subset differentiation in systemic autoimmunity. |
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| المؤلفون: | Pan W; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. Electronic address: wpan2@bidmc.harvard.edu., Tsokos MG; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Scherlinger M; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Rheumatology Department, Strasbourg University Hospital of Hautepierre, Strasbourg, France., Li W; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Tsokos GC; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. Electronic address: gtsokos@bidmc.harvard.edu. |
| المصدر: | Cell reports [Cell Rep] 2024 Jul 23; Vol. 43 (7), pp. 114379. Date of Electronic Publication: 2024 Jun 17. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | Autoimmunity* , Cell Differentiation* , Lupus Erythematosus, Systemic*/immunology , Lupus Erythematosus, Systemic*/pathology , NAD*/metabolism , NAD*/biosynthesis , Protein Phosphatase 2*/metabolism, Animals ; Female ; Humans ; Mice ; Forkhead Transcription Factors/metabolism ; Histones/metabolism ; Interferon-gamma/metabolism ; Interleukin-17/metabolism ; Lupus Nephritis/pathology ; Lupus Nephritis/immunology ; Lupus Nephritis/genetics ; Lupus Nephritis/metabolism ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Niacinamide/analogs & derivatives ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Pyridinium Compounds ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; Th17 Cells/metabolism |
| مستخلص: | The protein phosphatase 2A (PP2A) regulatory subunit PPP2R2A is involved in the regulation of immune response. We report that lupus-prone mice with T cells deficient in PPP2R2A display less autoimmunity and nephritis. PPP2R2A deficiency promotes NAD + biosynthesis through the nicotinamide riboside (NR)-directed salvage pathway in T cells. NR inhibits murine Th17 and promotes Treg cell differentiation, in vitro, by PΑRylating histone H1.2 and causing its reduced occupancy in the Foxp3 loci and increased occupancy in the Il17a loci, leading to increased Foxp3 and decreased Il17a transcription. NR treatment suppresses disease in MRL.lpr mice and restores NAD + -dependent poly [ADP-ribose] polymerase 1 (PARP1) activity in CD4 T cells from patients with systemic lupus erythematosus (SLE), while reducing interferon (IFN)-γ and interleukin (IL)-17 production. We conclude that PPP2R2A controls the level of NAD + through the NR-directed salvage pathway and promotes systemic autoimmunity. Translationally, NR suppresses lupus nephritis in mice and limits the production of proinflammatory cytokines by SLE T cells. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: CP: Immunology; CP: Metabolism; NAD(+); NR; PARP1; PP2A; PPP2R2A; Th17; Treg; histone H1.2; systemic lupus erythematosus |
| المشرفين على المادة: | 0 (Forkhead Transcription Factors) 0 (Histones) 82115-62-6 (Interferon-gamma) 0 (Interleukin-17) 0U46U6E8UK (NAD) 25X51I8RD4 (Niacinamide) 0I8H2M0L7N (nicotinamide-beta-riboside) EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) EC 3.1.3.16 (Protein Phosphatase 2) 0 (Pyridinium Compounds) EC 3.1.3.16 (Ppp2r2a protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240618 Date Completed: 20240729 Latest Revision: 20240731 |
| رمز التحديث: | 20240801 |
| DOI: | 10.1016/j.celrep.2024.114379 |
| PMID: | 38889006 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2024.114379 |