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Cited by 1,138interferon and immune responsesImmune Response and InflammationCytokine Signaling Pathways and Interactions

Shared and Distinct Functions of Type I and Type III Interferons

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Lazear, Helen M., Schoggins, John W., Diamond, Michael S.·2019·Immunity
DOI 10.1016/j.immuni.2019.03.025PMC PMC6839410
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Abstract

Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease.

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  • The wider footprints correspond to ISGF3 trimer binding and are consistent with the known structure and DNA contacts of ISGF3 and its subunits.

    “Together, these findings imply that the wider footprints (due to increased steric blockage of methylation at ISREs) correspond to ISGF3 trimer binding and are consistent with the known structure and DNA contacts of ISGF3 and its subunits40,41”

    From Single-molecule states link transcription factor binding to gene expression (2024) · cites this paper as [40]

    The IFN Signaling Pathways and the Antiviral Response section identifies ISGF3 as a heterotrimer of STAT1, STAT2, and IRF9 that binds ISREs. It does not discuss footprint width, methylation blockage, or the structural DNA contacts needed to link wider footprints specifically to ISGF3 binding. No page number is available in our copy. (LLM, conf=0.86)

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Authors
Lazear, H. M., Schoggins, J. W., & Diamond, M. S.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • The University of Texas Southwestern Medical Center (US)
  • Washington University in St. Louis (US)
Corresponding author
  • Lazear, Helen M.
  • Diamond, Michael S.
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2019-04
Volume
50
Issue
4
Pages
907-923
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2019.03.025
PMC
PMC6839410
OpenAlex
W2936804536
Cited by
1,138
References
5
Citations by year
2026: 124 · 2025: 170 · 2024: 191 · 2023: 156 · 2022: 150 · 2021: 192 · 2020: 117 · 2019: 35 · 2013: 2
FWCI
48.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
NIH (R01AI139512, DP2AI117922, R01AI073755, R01AI127828, R01HD091218)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
type I interferon, interferon lambda, interferon-alpha, interferon-beta, antiviral immunity, antitumor immunity, autoimmune disease, epithelial barrier function, interferon pathway, interferon therapy
MeSH terms
Interferon Lambda, Animals, Antiviral Agents, Autoimmune Diseases, Epithelial Cells, Female, Humans, Interferon Type I, Interferons, Male, Maternal-Fetal Exchange, Neoplasms, Organ Specificity, Pregnancy, Transcription, Genetic, Virus Diseases, Signal Transduction, Mice, Adaptive Immunity, Transcriptome

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