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Cited by 161Acute Myeloid Leukemia ResearchBlood disorders and treatmentsHematopoietic Stem Cell Transplantation

Clonal haematopoiesis and dysregulation of the immune system

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Belizaire, Roger, Wong, Waihay J., Robinette, Michelle L., Ebert, Benjamin L.·2023·Nature Reviews Immunology
DOI 10.1038/s41577-023-00843-3PMC PMC11140722
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Abstract

Age-related diseases are frequently linked to pathological immune dysfunction, including excessive inflammation, autoreactivity and immunodeficiency. Recent analyses of human genetic data have revealed that somatic mutations and mosaic chromosomal alterations in blood cells - a condition known as clonal haematopoiesis (CH) - are associated with ageing and pathological immune dysfunction. Indeed, large-scale epidemiological studies and experimental mouse models have demonstrated that CH can promote cardiovascular disease, chronic obstructive pulmonary disease, chronic liver disease, osteoporosis and gout. The genes most frequently mutated in CH, the epigenetic regulators TET2 and DNMT3A, implicate increased chemokine expression and inflammasome hyperactivation in myeloid cells as a possible mechanistic connection between CH and age-related diseases. In addition, TET2 and DNMT3A mutations in lymphoid cells have been shown to drive methylation-dependent alterations in differentiation and function. Here we review the observational and mechanistic studies describing the connection between CH and pathological immune dysfunction, the effects of CH-associated genetic alterations on the function of myeloid and lymphoid cells, and the clinical and therapeutic implications of CH as a target for immunomodulation.

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Authors
Belizaire, R., Wong, W. J., Robinette, M. L., & Ebert, B. L.
Affiliations
  • Dana-Farber Cancer Institute (US)
  • Brigham and Women's Hospital (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Ebert, Benjamin L.
ORCID
Venue
Nature Reviews Immunology
Publisher
Springer Science and Business Media LLC
Published
2023-03-20
Volume
23
Issue
9
Pages
595-610
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
DOI
10.1038/s41577-023-00843-3
PMC
PMC11140722
OpenAlex
W4328048447
Cited by
161
References
31
Citations by year
2026: 42 · 2025: 57 · 2024: 42 · 2023: 18 · 2022: 1
FWCI
8.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R35CA253125, K08CA258803)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
clonal hematopoiesis, somatic mutations, mosaic chromosomal alterations, age-related diseases, immune dysfunction, TET2, DNMT3A, myeloid cells, lymphoid cells, autoimmunity, immunodeficiency, inflammation, epigenetic regulation, DNA methylation, chemokine expression, inflammasome, cardiovascular disease, chronic obstructive pulmonary disease, chronic liver disease, osteoporosis, gout, immunomodulation
MeSH terms
Clonal Hematopoiesis, DNA Methyltransferase 3A, Animals, DNA (Cytosine-5-)-Methyltransferases, Hematopoiesis, Humans, Immune System, Mutation, Mice

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