Cited by 352Cytokine Signaling Pathways and InteractionsT-cell and B-cell ImmunologyImmune cells in cancer

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Regulation of inflammation by interleukin-4: a review of "alternatives"

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Luzina, Irina G, Keegan, Achsah D, Heller, Nicola M, Rook, Graham A W, Shea-Donohue, Terez, Atamas, Sergei P·2012·Journal of Leukocyte Biology

DOI 10.1189/jlb.0412214PMC PMC3441310

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Abstract

Studies of IL-4 have revealed a wealth of information on the diverse roles of this cytokine in homeostatic regulation and disease pathogenesis. Recent data suggest that instead of simple linear regulatory pathways, IL-4 drives regulation that is full of alternatives. In addition to the well-known dichotomous regulation of Th cell differentiation by IL-4, this cytokine is engaged in several other alternative pathways. Its own production involves alternative mRNA splicing, yielding at least two functional isoforms: full-length IL-4, encoded by the IL-4 gene exons 1-4, and IL-4δ2, encoded by exons 1, 3, and 4. The functional effects of these two isoforms are in some ways similar but in other ways quite distinct. When binding to the surface of target cells, IL-4 may differentially engage two different types of receptors. By acting on macrophages, a cell type critically involved in inflammation, IL-4 induces the so-called alternative macrophage activation. In this review, recent advances in understanding these three IL-4-related branch points--alternative splicing of IL-4, differential receptor engagement by IL-4, and differential regulation of macrophage activation by IL-4--are summarized in light of their contributions to inflammation.

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Authors: Luzina, I. G., Keegan, A. D., Heller, N. M., Rook, G. A. W., Shea-Donohue, T., & Atamas, S. P.
Affiliations: University of Maryland, Baltimore (US)
Johns Hopkins University (US)
University College London (GB)
University of Maryland School of Medicine , Baltimore, Maryland, USA
Corresponding author: Atamas, Sergei P
ORCID: Keegan, Achsah D
Heller, Nicola M
Rook, Graham A W
Atamas, Sergei P
Venue: Journal of Leukocyte Biology
Publisher: Oxford University Press (OUP)
Published: 2012-10-01
Volume: 92
Issue: 4
Pages: 753-764
ISSN: 0741-5400 (ISSN-L)
1938-3673
DOI: 10.1189/jlb.0412214
PMC: PMC3441310
OpenAlex: W2103125300
Cited by: 351
References: 189
Citations by year: 2026: 9 · 2025: 18 · 2024: 24 · 2023: 38 · 2022: 28 · 2021: 53 · 2020: 30 · 2019: 28 · 2018: 28 · 2017: 23 · 2016: 19 · 2015: 18 · 2014: 22 · 2013: 11 · 2012: 2
FWCI: 1.75
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: Journal of Leukocyte Biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: VA Merit Award (5I01CX000101, 5I01CX000107)
U.S. National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R03AR054946)
NIAID (RO1AI038985, 2RO1AI049316)
National Heart, Lung, and Blood Institute (1R21HL106196)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: IL-4, inflammation, alternative mRNA splicing, T helper cell differentiation, macrophage activation, alternative macrophage activation, IL-4 receptor, cytokine signaling
MeSH terms: Animals, Asthma, Humans, Inflammation, Macrophage Activation, Scleroderma, Systemic, Tuberculosis, Signal Transduction, Interleukin-4, Receptors, Interleukin-4, Receptors, Interleukin-13, Protein Tyrosine Phosphatase, Non-Receptor Type 6

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Regulation of inflammation by interleukin-4: a review of "alternatives"

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