Fasting-induced FOXO4 blunts human CD4 + T helper cell responsiveness.

التفاصيل البيبلوغرافية
العنوان: Fasting-induced FOXO4 blunts human CD4 + T helper cell responsiveness.
المؤلفون: Han K; Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Singh K; Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.; Bioinformatics and Computational Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Rodman MJ; Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Hassanzadeh S; Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Wu K; Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Nguyen A; Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Huffstutler RD; Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Seifuddin F; Bioinformatics and Computational Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Dagur PK; Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Saxena A; Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., McCoy JP; Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Chen J; Center of Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Biancotto A; Center of Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Department of Precision Immunology, Sanofi, Cambridge, MA, USA., Stagliano KER; Center of Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Teague HL; Laboratory of Cardiometabolic Disease and Inflammation, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Mehta NN; Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.; Laboratory of Cardiometabolic Disease and Inflammation, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Pirooznia M; Bioinformatics and Computational Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA., Sack MN; Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. sackm@nih.gov.; Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. sackm@nih.gov.
المصدر: Nature metabolism [Nat Metab] 2021 Mar; Vol. 3 (3), pp. 318-326. Date of Electronic Publication: 2021 Mar 15.
نوع المنشور: Letter; Research Support, N.I.H., Intramural
اللغة: English
بيانات الدورية: Publisher: Springer Nature Country of Publication: Germany NLM ID: 101736592 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2522-5812 (Electronic) Linking ISSN: 25225812 NLM ISO Abbreviation: Nat Metab Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Berlin : Springer Nature, [2019]-
مواضيع طبية MeSH: Fasting*, Cell Cycle Proteins/*biosynthesis , Forkhead Transcription Factors/*biosynthesis , T-Lymphocytes, Helper-Inducer/*immunology, Gene Expression Regulation ; Humans ; Sequence Analysis, RNA
مستخلص: Intermittent fasting blunts inflammation in asthma 1 and rheumatoid arthritis 2 , suggesting that fasting may be exploited as an immune-modulatory intervention. However, the mechanisms underpinning the anti-inflammatory effects of fasting are poorly characterized 3-5 . Here, we show that fasting in humans is sufficient to blunt CD4 + T helper cell responsiveness. RNA sequencing and flow cytometry immunophenotyping of peripheral blood mononuclear cells from volunteers subjected to overnight or 24-h fasting and 3 h of refeeding suggest that fasting blunts CD4 + T helper cell activation and differentiation. Transcriptomic analysis reveals that longer fasting has a more robust effect on CD4 + T-cell biology. Through bioinformatics analyses, we identify the transcription factor FOXO4 and its canonical target FK506-binding protein 5 (FKBP5) as a potential fasting-responsive regulatory axis. Genetic gain- or loss-of-function of FOXO4 and FKBP5 is sufficient to modulate T H 1 and T H 17 cytokine production. Moreover, we find that fasting-induced or genetic overexpression of FOXO4 and FKBP5 is sufficient to downregulate mammalian target of rapamycin complex 1 signalling and suppress signal transducer and activator of transcription 1/3 activation. Our results identify FOXO4-FKBP5 as a new fasting-induced, signal transducer and activator of transcription-mediated regulatory pathway to blunt human CD4 + T helper cell responsiveness.
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معلومات مُعتمدة: ZIA HL005102 United States ImNIH Intramural NIH HHS; ZIA HL005199 United States ImNIH Intramural NIH HHS; ZIC HL006199 United States ImNIH Intramural NIH HHS
سلسلة جزيئية: ClinicalTrials.gov NCT02719899; NCT01143454; NCT00001846
المشرفين على المادة: 0 (Cell Cycle Proteins)
0 (FOXO4 protein, human)
0 (Forkhead Transcription Factors)
تواريخ الأحداث: Date Created: 20210316 Date Completed: 20210423 Latest Revision: 20221027
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7990708
DOI: 10.1038/s42255-021-00356-0
PMID: 33723462
قاعدة البيانات: MEDLINE
الوصف
تدمد:2522-5812
DOI:10.1038/s42255-021-00356-0