دورية أكاديمية
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Adipose cDC1s contribute to obesity-associated inflammation through STING-dependent IL-12 production.

التفاصيل البيبلوغرافية
العنوان: Adipose cDC1s contribute to obesity-associated inflammation through STING-dependent IL-12 production.
المؤلفون: Hildreth AD; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA., Padilla ET; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Gupta M; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Wong YY; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Sun R; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Legala AR; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., O'Sullivan TE; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. tosullivan@mednet.ucla.edu.; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA. tosullivan@mednet.ucla.edu.
المصدر: Nature metabolism [Nat Metab] 2023 Dec; Vol. 5 (12), pp. 2237-2252. Date of Electronic Publication: 2023 Nov 23.
نوع المنشور: Journal Article
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: Obesity*/metabolism , Insulin Resistance*, Animals ; Humans ; Adipose Tissue/metabolism ; Adiposity/genetics ; Inflammation/metabolism ; Interleukin-12/metabolism ; Mammals/metabolism
مستخلص: Obesity is associated with chronic low-grade white adipose tissue (WAT) inflammation that can contribute to the development of insulin resistance in mammals. Previous studies have identified interleukin (IL)-12 as a critical upstream regulator of WAT inflammation and metabolic dysfunction during obesity. However, the cell types and mechanisms that initiate WAT IL-12 production remain unclear. Here we show that conventional type 1 dendritic cells (cDC1s) are the cellular source of WAT IL-12 during obesity through analysis of mouse and human WAT single-cell transcriptomic datasets, IL-12 reporter mice and IL-12p70 protein levels by enzyme-linked immunosorbent assay. We demonstrate that cDC1s contribute to obesity-associated inflammation by increasing group 1 innate lymphocyte interferon-γ production and inflammatory macrophage accumulation. Inducible depletion of cDC1s increased WAT insulin sensitivity and systemic glucose tolerance during diet-induced obesity. Mechanistically, endocytosis of apoptotic bodies containing self-DNA by WAT cDC1s drives stimulator of interferon genes (STING)-dependent IL-12 production. Together, these results suggest that WAT cDC1s act as critical regulators of adipose tissue inflammation and metabolic dysfunction during obesity.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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معلومات مُعتمدة: F31DK130585 U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
المشرفين على المادة: 187348-17-0 (Interleukin-12)
تواريخ الأحداث: Date Created: 20231123 Date Completed: 20231221 Latest Revision: 20240122
رمز التحديث: 20240123
DOI: 10.1038/s42255-023-00934-4
PMID: 37996702
قاعدة البيانات: MEDLINE
الوصف
تدمد:2522-5812
DOI:10.1038/s42255-023-00934-4