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Cited by 928Cytokine Signaling Pathways and InteractionsT-cell and B-cell Immunologyinterferon and immune responses

Cross-regulation of Signaling Pathways by Interferon-γ: Implications for Immune Responses and Autoimmune Diseases

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Hu, Xiaoyu, Ivashkiv, Lionel B.·2009·Immunity
DOI 10.1016/j.immuni.2009.09.002PMC PMC2774226
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Abstract

Interferon-gamma (IFN-gamma) is an important mediator of immunity and inflammation that utilizes the JAK-STAT signaling pathway to activate the STAT1 transcription factor. Many functions of IFN-gamma have been ascribed to direct STAT1-mediated induction of immune effector genes, but recently it has become clear that key IFN-gamma functions are mediated by cross-regulation of cellular responses to other cytokines and inflammatory factors. Here, we review mechanisms by which IFN-gamma and STAT1 regulate signaling by Toll-like receptors, inflammatory factors, tissue-destructive cytokines, anti-inflammatory cytokines, and cytokines that activate opposing STATs. These signaling mechanisms reveal insights about how IFN-gamma regulates macrophage activation, inflammation, tissue remodeling, and helper and regulatory T cell differentiation and how Th1 and Th17 cell responses are integrated in autoimmune diseases.

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  • IFNγ and IL-17 can cross-regulate each other.

    “Since IFNγ and IL-17 can cross-regulate each other [20] and IL-17 is critical for host defense against C. auris [6], we hypothesized if increased IFNγ diminishes protective IL-17 response and increases fungal burden during C. auris-infection.”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [20]

    In “Regulation of adaptive immunity: Th and Treg differentiation” (page unavailable), the review says IFN-γ suppresses Th17 differentiation and inhibits Th17-cell effector functions. It does not establish the reverse—that IL-17 regulates IFN-γ—so the claim’s reciprocal wording is not fully supported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Authors
Hu, X., & Ivashkiv, L. B.
Affiliations
Hospital for Special Surgery (US)
Corresponding author
Ivashkiv, Lionel B.
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2009-10
Volume
31
Issue
4
Pages
539-550
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2009.09.002
PMC
PMC2774226
OpenAlex
W2037299986
Cited by
928
References
6
Citations by year
2026: 71 · 2025: 76 · 2024: 70 · 2023: 66 · 2022: 69 · 2021: 83 · 2020: 59 · 2019: 44 · 2018: 47 · 2017: 47 · 2016: 40 · 2015: 45 · 2014: 45 · 2013: 44 · 2012: 50
FWCI
3.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (2r01ai046712-26)
  • National Institute of Allergy and Infectious Diseases (R01-AI046712, R01AI059636, R01AI044938)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050401, R01AR046713)
  • National Institute of Dental and Craniofacial Research (R01DE019420)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
interferon-gamma, STAT1, JAK/STAT signaling, Toll-like receptors, macrophage activation, inflammation, tissue remodeling, regulatory T cells, Th1 cells, Th17 cells, autoimmune disease, cytokine signaling, anti-inflammatory cytokines
MeSH terms
Animals, Autoimmune Diseases, Humans, Immunity, Active, Immunity, Innate, Interferon-gamma, Protein Kinases, Signal Transduction, T-Lymphocyte Subsets, Cytokines, STAT Transcription Factors, Toll-Like Receptors

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