CoChat
Sign Up
Cited by 393T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisGenomics and Chromatin Dynamics

Gata-3 Induces T Helper Cell Type 2 (Th2) Cytokine Expression and Chromatin Remodeling in Committed Th1 Cells

Open access
Lee, Hyun Jun, Takemoto, Naofumi, Kurata, Hirokazu, Kamogawa, Yumiko, Miyatake, Shoichiro, O'Garra, Anne, Arai, Naoko·2000·The Journal of Experimental Medicine
DOI 10.1084/jem.192.1.105PMC PMC1887713
Open this paper in CoChat — free account

Abstract

Committed T helper type 1 (Th1) and Th2 effector cells, resulting from chronic antigenic stimulation in interleukin (IL)-12 and IL-4, are implicated in the pathology of autoimmune and allergic diseases. Committed Th1 cells cannot be induced to change their cytokine profiles in response to antigenic stimulation and Th2 cytokine–inducing conditions. Here, we report that ectopic expression of GATA-3 induced Th2-specific cytokine expression not only in developing Th1 cells but also in otherwise irreversibly committed Th1 cells and a Th1 clone, HDK1. Moreover, cAMP, an inhibitor of cytokine production by Th1 cells, markedly augmented Th2 cytokine production in GATA-3–expressing Th1 cells. Ectopic expression of GATA-3 in developing Th1 cells, but not in Th1 clone HDK1, induced endogenous GATA-3, suggesting an autoregulatory mechanism for maintenance of GATA-3 expression in Th2 cells. Structure–function analyses of GATA-3 revealed that the NH2-terminal transactivation domain and the COOH-terminal zinc finger domain of GATA-3 were critical, whereas the NH2-terminal zinc finger domain was dispensable for the induction of IL-4. Both zinc fingers, however, were required for IL-5 induction. A Th2-specific DNaseI-hypersensitive site of the IL-4 locus was detected in GATA-3–expressing Th1 cells. Thus, GATA-3 can change the phenotype of committed Th1 cells, previously considered to be irreversible.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.192.1.105

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • SNS outflow in depression may suppress transcription of antiviral immune response genes, leading to increased susceptibility to viruses.

    “the SNS outflow that occurs in depression (see Irwin et al., 1991) may suppress transcription of antiviral immune response genes (S. W. Cole et al., 1998; Lee et al., 2000), leading to increased susceptibility to viruses”

    From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Lee et al., 2000

    The Results section reports that cAMP treatment decreased IFN-γ production in a Th1 cell clone, but not in three-week polarized Th1 cells. The paper does not connect this finding to sympathetic nervous system outflow, depression, suppression of antiviral gene transcription, or increased susceptibility to viruses. No page numbers are available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Adrenergic signaling suppresses transcription of antiviral type I IFN genes and up-regulates transcription of proinflammatory immune response genes IL1, TNF, and IL6, leading to increases in systemic inflammatory activity.

    “This adrenergic signaling cascade suppresses transcription of antiviral type I IFN genes”

    From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Lee et al., 2000

    The Discussion (page not provided) addresses cAMP and GATA-3 effects on Th1/Th2 cytokines, including IFN-γ, not adrenergic suppression of type I IFN genes. Searches for adrenergic signaling, antiviral type I IFN, and IL1/TNF/IL6-driven systemic inflammation found no passage addressing the attributed claim. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 72 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Murphy K.M. Heimberger A.B. Loh D.Y. Induction by antigen of interthymic apoptosis of CD4+ CD8+ TCRlo thymocytes in vivo Science. 250 1990 1720 1722 2125367

Cited by

Sorted by citations

Related

Authors
Lee, H. J., Takemoto, N., Kurata, H., Kamogawa, Y., Miyatake, S., O'Garra, A., & Arai, N.
Affiliations
  • aDepartment of Immunology, DNAX Research Institute, Palo Alto, California 94304-1104
  • Institute of Medical Science, The University of Tokyo (JP)
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2000-07-03
Volume
192
Issue
1
Pages
105-116
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.192.1.105
PMC
PMC1887713
OpenAlex
W2119767265
Cited by
393
References
72
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 1 · 2021: 9 · 2020: 7 · 2019: 4 · 2018: 11 · 2017: 7 · 2016: 13 · 2015: 8 · 2014: 22 · 2013: 13 · 2012: 9
FWCI
10.63
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
GATA3, Th1 cells, Th2 cytokines, IL-4, IL-5, chromatin remodeling, DNase I hypersensitive sites, cyclic AMP, zinc finger, transactivation domain, T helper cell differentiation, cytokine gene expression
MeSH terms
Animals, Cells, Cultured, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Genetic Vectors, Interferon-gamma, Mice, Inbred BALB C, Moloney murine leukemia virus, Recombinant Proteins, Transfection, CD4-Positive T-Lymphocytes, Trans-Activators, Interleukin-4, Interleukin-5, Cytokines, Zinc Fingers, Th1 Cells, Th2 Cells, GATA3 Transcription Factor, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review