Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Itch expression by Treg cells controls Th2 inflammatory responses
Hyung-seung Jin, … , Chris Elly, Yun-Cai Liu
Hyung-seung Jin, … , Chris Elly, Yun-Cai Liu
Published October 25, 2013
Citation Information: J Clin Invest. 2013;123(11):4923-4934. https://doi.org/10.1172/JCI69355.
View: Text | PDF
Research Article

Itch expression by Treg cells controls Th2 inflammatory responses

  • Text
  • PDF
Abstract

Regulatory T (Treg) cells maintain immune homeostasis by limiting autoimmune and inflammatory responses. Treg differentiation, maintenance, and function are controlled by the transcription factor Foxp3. However, the exact molecular mechanisms underlying Treg cell regulation remain elusive. Here, we show that Treg cell–specific ablation of the E3 ubiquitin ligase Itch in mice caused massive multiorgan lymphocyte infiltration and skin lesions, chronic T cell activation, and the development of severe antigen-induced airway inflammation. Surprisingly, Foxp3 expression, homeostasis, and the in vitro and in vivo suppressive capability of Treg cells were not affected by Itch deficiency. We found that the expression of Th2 cytokines by Treg cells was increased in the absence of Itch. Fate mapping revealed that a fraction of Treg cells lost Foxp3 expression independently of Itch. However, Th2 cytokines were excessively augmented in Itch–/– Foxp3-negative “ex-Treg” cells without altering the percentage of conversion. Targeted knockdown of Th2 transcriptional regulators in Itch–/– Treg cells prevented Th2 cytokine production. The present study unveils a mechanism of Treg cell acquisition of Th2-like properties that is independent of Foxp3 function and Treg cell stability.

Authors

Hyung-seung Jin, Yoon Park, Chris Elly, Yun-Cai Liu

×

Figure 8

Itch-deficient Treg cells instruct the differentiation of naive T cells into Th2 in vitro.

Options: View larger image (or click on image) Download as PowerPoint
Itch-deficient Treg cells instruct the differentiation of naive T cells ...
(A–C) FACS-sorted CD62Lhi CD44lo naive CD4+ T cells were cultured with supernatants (sup) from wild-type or Itch-deficient Treg cells for 5 days. Anti–IL-4 antibodies were added where indicated. (A) IL-4– and IFN-γ–producing cells were analyzed by intracellular cytokine staining 5 hours after restimulation with anti-CD3/CD28 antibodies. Data are representative of three independent experiments. (B and C) RT-PCR analysis of the indicated genes in these cells is shown. Data are compiled from three independent experiments. Error bars indicate the mean ± SD. **P < 0.01; ***P < 0.001 (unpaired 2-tailed Student’s t test).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts