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Cited by 76Hematopoietic Stem Cell Transplantationinterferon and immune responsesBlood disorders and treatments

Yin and Yang: The dual effects of interferons on hematopoiesis

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Demerdash, Yasmin, Kain, Bailee, Essers, Marieke A.G., King, Katherine Y.·2021·Experimental Hematology
DOI 10.1016/j.exphem.2021.02.002PMC PMC8919039
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Abstract

Interferons are an ancient and well-conserved group of inflammatory cytokines most famous for their role in viral immunity. A decade ago, we discovered that interferons also play an important role in the biology of hematopoietic stem cells (HSCs), which are responsible for lifelong blood production. Though we have learned a great deal about the role of interferons on HSC quiescence, differentiation, and self-renewal, there remains some controversy regarding how interferons impact these stem cells, with differing conclusions depending on experimental models and clinical context. Here, we review the contradictory roles of Type 1 and 2 interferons in hematopoiesis. Specifically, we highlight the roles of interferons in embryonic and adult hematopoiesis, along with short-term and long-term adaptive and maladaptive responses to inflammation. We discuss experimental challenges in the study of these powerful yet short-lived cytokines and strategies to address those challenges. We further review the contribution by interferons to disease states including bone marrow failure and aplastic anemia as well as their therapeutic use to treat myeloproliferative neoplasms and viral infections, including SARS-CoV2. Understanding the opposing effects of interferons on hematopoiesis will elucidate immune responses and bone marrow failure syndromes, and future therapeutic approaches for patients undergoing HSC transplantation or fighting infectious diseases and cancer.

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  • The mouse experiments recapitulate chronic inflammation through induction of multiple pro-inflammatory cytokines known to be increased in the serum of patients with MPN, including IFNγ.

    “These experiments recapitulate chronic inflammation through induction of multiple pro-inflammatory cytokines34,35 known to be increased in the serum of patients with MPN36, including IFNγ (Fig. 5a and Extended Data Fig. 10a).”

    From Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution (2023) · cites this paper as [34]

    The Introduction’s section on short- versus long-term interferon signaling describes persistent IFNγ signaling in mouse infection models, supporting the inflammatory IFNγ component. It does not establish that the citing paper’s mouse experiments induced multiple pro-inflammatory cytokines or recapitulated chronic inflammation in that way. The separate claim about cytokines in MPN patient serum is attached to citation 36, not this source. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Demerdash, Y., Kain, B., Essers, M. A. G., & King, K. Y.
Affiliations
  • German Cancer Research Center (DE)
  • Baylor College of Medicine (US)
Corresponding author
King, Katherine Y.
ORCID
Venue
Experimental Hematology
Publisher
Elsevier BV
Published
2021-04
Volume
96
Pages
1-12
ISSN
0301-472X (ISSN-L)
DOI
10.1016/j.exphem.2021.02.002
PMC
PMC8919039
OpenAlex
W3127942821
Cited by
76
References
5
Citations by year
2026: 14 · 2025: 15 · 2024: 12 · 2023: 16 · 2022: 13 · 2021: 6
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Experimental Hematology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart Lung and Blood Institute
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • German Research Foundation
  • Dietmar Hopp Foundation
  • National Institute of Allergy and Infectious Diseases
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
Keywords
interferon, hematopoiesis, hematopoietic stem cells, type I interferon, HSC quiescence, HSC differentiation, HSC self-renewal, embryonic hematopoiesis, inflammation, bone marrow failure, aplastic anemia, myeloproliferative neoplasms, SARS-CoV-2, HSC transplantation, antiviral immunity
MeSH terms
Animals, Antineoplastic Agents, Hematopoiesis, Hematopoietic Stem Cells, Humans, Immunologic Factors, Interferons, Hematologic Neoplasms

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