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Cited by 474T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisCytokine Signaling Pathways and Interactions

Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages

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Liao, Wei, Lin, Jian-Xin, Wang, Lu, Li, Peng, Leonard, Warren J·2011·Nature Immunology
DOI 10.1038/ni.2030PMC PMC3304099
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Abstract

Helper T cells control host defense against pathogens. The receptors for interleukin 12 (IL-12), IL-4 and IL-6 are required for differentiation into the T(H)1, T(H)2 and T(H)17 subsets of helper T cells, respectively. IL-2 signaling via the transcription factor STAT5 controls T(H)2 differentiation by regulating both the T(H)2 cytokine gene cluster and expression of Il4ra, the gene encoding the IL-4 receptor α-chain. Here we show that IL-2 regulated T(H)1 differentiation, inducing STAT5-dependent expression of the IL-12 receptor β2-chain (IL-12Rβ2) and the transcription factor T-bet, with impaired human T(H)1 differentiation when IL-2 was blocked. T(H)1 differentiation was also impaired in mouse Il2(-/-) T cells but was restored by IL-12Rβ2 expression. Consistent with the inhibition of T(H)17 differentiation by IL-2, treatment with IL-2 resulted in lower expression of the genes encoding the IL-6 receptor α-chain (Il6ra) and the IL-6 signal transducer gp130 (encoded by Il6st), and retroviral transduction of Il6st augmented T(H)17 differentiation even when IL-2 was present. Thus, IL-2 influences helper T cell differentiation by modulating the expression of cytokine receptors to help specify and maintain differentiated states.

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Authors
Liao, W., Lin, J.-X., Wang, L., Li, P., & Leonard, W. J.
Affiliations
National Institutes of Health (US)
Corresponding author
Leonard, Warren J
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2011-04-24
Volume
12
Issue
6
Pages
551-559
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.2030
PMC
PMC3304099
OpenAlex
W2020304403
Cited by
474
References
2
Citations by year
2026: 7 · 2025: 34 · 2024: 33 · 2023: 34 · 2022: 34 · 2021: 29 · 2020: 26 · 2019: 18 · 2018: 27 · 2017: 41 · 2016: 36 · 2015: 37 · 2014: 36 · 2013: 44 · 2012: 26
FWCI
16.75
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (ZIAHL005401, ZIAHL005402)
  • National Institute of Allergy and Infectious Diseases
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
interleukin-2, T helper cell differentiation, STAT5, IL-12 receptor beta 2, T-bet, gp130, IL-4 receptor alpha, cytokine receptors, T cell lineage specification
MeSH terms
T-bet Transcription Factor, Animals, Cell Differentiation, Cells, Cultured, Flow Cytometry, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Humans, Interleukin-2, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Cytokine, Mice, Knockout, Th1 Cells, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, T-Box Domain Proteins, Gene Expression Profiling, Cell Proliferation, STAT5 Transcription Factor, Mice, Receptors, Interleukin-12, Mice, 129 Strain, HEK293 Cells

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