The DOI matches its Crossref record; 184 of the 189 references it cites were found in a registry or an index.
Regulation of inflammation by interleukin-4: a review of "alternatives"
Open accessAbstract
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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“previous studies have shown that phosphorylation of STAT6 is a key step downstream in the IL-4 cascade that leads to Arg1 expression (49–51).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [49]
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Metadata
- 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
- 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
- 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
- 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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