Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss.

DNMT3A T cells arthritis bone marrow clonal hematopoiesis of indeterminate potential hematopoietic stem and progenitor cells inflammation neutrophils osteoclastogenesis periodontitis

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
30 May 2024
Historique:
received: 23 08 2023
revised: 19 02 2024
accepted: 01 05 2024
medline: 6 6 2024
pubmed: 6 6 2024
entrez: 5 6 2024
Statut: aheadofprint

Résumé

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3a

Identifiants

DOI: 10.1016/j.cell.2024.05.003 PMID: 38838669
pubmed: 38838669
pii: S0092-8674(24)00492-6
doi: 10.1016/j.cell.2024.05.003
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests P.N. reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio, scientific co-founder of TenSixteen Bio, equity in MyOme, Preciseli, and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. M.G.N. is an advisory board member of Cell and scientific founder of Lemba, TTxD, and Biotrip.

Auteurs

Hui Wang (H)

Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Kimon Divaris (K)

Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.

Bohu Pan (B)

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.

Xiaofei Li (X)

Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Shanghai Jiao Tong University, School of Life Sciences and Biotechnology, Sheng Yushou Center of Cell Biology and Immunology, Shanghai 200240, China.

Jong-Hyung Lim (JH)

Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Gundappa Saha (G)

Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Marko Barovic (M)

Institute for Clinical Chemistry and Laboratory Medicine, University Hospital, Technische Universität Dresden, 01307 Dresden, Germany.

Danai Giannakou (D)

Institute for Clinical Chemistry and Laboratory Medicine, University Hospital, Technische Universität Dresden, 01307 Dresden, Germany.

Jonathan M Korostoff (JM)

Department of Periodontics, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Yu Bing (Y)

Human Genetics Center, Department of Epidemiology, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Souvik Sen (S)

Department of Neurology, University of South Carolina, Columbia, SC 29209, USA; Center for the Study of Aphasia Recovery, University of South Carolina, Columbia, SC 29209, USA.

Kevin Moss (K)

Department of Biostatistics and Health Data Sciences, School of Medicine, Indiana University, Indianapolis, IN 46202, USA; Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.

Di Wu (D)

Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.

James D Beck (JD)

Division of Comprehensive Oral Health-Periodontology, Adams School of Dentistry, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.

Christie M Ballantyne (CM)

Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

Pradeep Natarajan (P)

Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02141, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

Kari E North (KE)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.

Mihai G Netea (MG)

Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 XZ Nijmegen, the Netherlands; Department of Immunology and Metabolism, LIMES, University of Bonn, 53115 Bonn, Germany.

Triantafyllos Chavakis (T)

Institute for Clinical Chemistry and Laboratory Medicine, University Hospital, Technische Universität Dresden, 01307 Dresden, Germany.

George Hajishengallis (G)

Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: geoh@upenn.edu.

Classifications MeSH