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Cited by 433interferon and immune responsesInflammasome and immune disordersAutoimmune and Inflammatory Disorders Research

Type I interferon–mediated monogenic autoinflammation: The type I interferonopathies, a conceptual overview

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Rodero, Mathieu P., Crow, Yanick J.·2016·Journal of Experimental Medicine
DOI 10.1084/jem.20161596PMC PMC5110029
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Abstract

Type I interferon is a potent substance. As such, the induction, transmission, and resolution of the type I interferon–mediated immune response are tightly regulated. As defined, the type I interferonopathies represent discrete examples of a disturbance of the homeostatic control of this system caused by Mendelian mutations. Considering the complexity of the interferon response, the identification of further monogenic diseases belonging to this disease grouping seems likely, with the recognition of type I interferonopathies becoming of increasing clinical importance as treatment options are developed based on an understanding of disease pathology and innate immune signaling. Definition of the type I interferonopathies indicates that autoinflammation can be both interferon and noninterferon related, and that a primary disturbance of the innate immune system can “spill over” into autoimmunity in some cases. Indeed, that several non-Mendelian disorders, most particularly systemic lupus erythematosus and dermatomyositis, are also characterized by an up-regulation of type I interferon signaling suggests the possibility that insights derived from this work will have relevance to a broader field of clinical medicine.

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  • People with DS present increased IFN signaling likely driven by triplication of four of the six IFN receptors encoded on HSA21, rather than by massive elevation of IFN ligands, and this has been associated with chronic immune dysregulation.

    “people with DS present an increased IFN signaling likely driven by triplication of four of the six IFN receptors encoded on HSA21,36 rather than by massive elevation of the IFN ligands themselves as seen in interferonopathies,80 and this has been associated with chronic immune dysregulation.”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [80]

    The citation is attached to the comparison with interferonopathies, not to the Down syndrome receptor-triplication claim. In “Is it appropriate to use the term type I interferonopathies (I)?” (page unavailable), the paper says circulating interferons are likely present at low levels and are difficult to measure directly; it does not describe massive elevation of IFN ligands in interferonopathies. It instead uses interferon-stimulated genes as a measure of increased signaling. (LLM, conf=0.86)

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  • Inappropriate upregulation of type I IFN signaling and ISG expression in the CNS has been linked to several interferonopathies including Aicardi-Goutieres syndrome and USP18-deficiency in humans.

    “Inappropriate upregulation of type I IFN signaling and ISG expression in the CNS have been linked to several interferonopathies including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)-deficiency in humans.”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [80]

    The sections “Which diseases should be considered as type I interferonopathies?” and “Is it appropriate to use the term type I interferonopathies (II)?” link AGS and USP18 deficiency to enhanced interferon signaling, and report elevated cerebrospinal-fluid interferon activity in AGS. They do not establish upregulated ISG expression specifically in the CNS of humans with both conditions. No page numbers are available in our copy. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Rodero, M. P., & Crow, Y. J.
Affiliations
  • Inserm (FR)
  • Hôpital Necker-Enfants Malades (FR)
Corresponding author
Crow, Yanick J.
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2016-11-07
Volume
213
Issue
12
Pages
2527-2538
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20161596
PMC
PMC5110029
OpenAlex
W2556737993
Cited by
433
References
5
Citations by year
2026: 27 · 2025: 25 · 2024: 36 · 2023: 41 · 2022: 45 · 2021: 63 · 2020: 67 · 2019: 36 · 2018: 55 · 2017: 37 · 2016: 1
FWCI
4.15
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-sa)
  • HAL (submittedVersion, other-oa)
Funders
  • European Research Council (GA 309449, MR/M501803/1)
  • National Research Agency (ANR-10-IAHU-01)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords
type I interferonopathy, type I interferon, innate immune signaling, autoimmunity, systemic lupus erythematosus, dermatomyositis
MeSH terms
Animals, Humans, Inflammation, Interferon Type I, Models, Biological, Phenotype, Autoimmunity, Penetrance

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