The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain
Abstract
Several novel interleukin (IL)-10-related cytokines have recently been discovered. These include IL-22, IL-26, and the interferon-λ (IFN-λ) proteins IFN-λ1 (IL-29), IFN-λ2 (IL-28A), and IFN-λ3 (IL-28B). The ligand-binding chains for IL-22, IL-26, and IFN-λ are distinct from that used by IL-10; however, all of these cytokines use a common second chain, IL-10 receptor-2 (IL-10R2; CRF2-4), to assemble their active receptor complexes. Thus, IL-10R2 is a shared component in at least four distinct class II cytokine-receptor complexes. IL-10 binds to IL-10R1; IL-22 binds to IL-22R1; IL-26 binds to IL-20R1; and IFN-λ binds to IFN-λR1 (also known as IL-28R). The binding of these ligands to their respective R1 chains induces a conformational change that enables IL-10R2 to interact with the newly formed ligand-receptor complexes. This in turn activates a signal-transduction cascade that results in rapid activation of several transcription factors, particularly signal transducer and activator of transcription (STAT)3 and to a lesser degree, STAT1. Activation by IL-10, IL-22, IL-26, or IFN-λ can be blocked with neutralizing antibodies to the IL-10R2 chain. Although IL-10R2 is broadly expressed on a wide variety of tissues, only a subset of these tissues expresses the ligand-binding R1 chains. The receptors for these cytokines are often present on cell lines derived from various tumors, including liver, colorectal, and pancreatic carcinomas. Consequently, the receptors for these cytokines may provide novel targets for inhibiting the growth of certain types of cancer.
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β2 agonists have been shown to reduce bacterium- and toxin-induced epithelial cell damage in models of nasal epithelial culture.
“β2 agonists have been shown to reduce bacterium- and toxin-induced epithelial cell damage in models of nasal epithelial culture (53, 54).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [53]
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- Authors
- Donnelly, R. P., Sheikh, F., Kotenko, S. V., & Dickensheets, H.
- Affiliations
- United States Food and Drug Administration (US)
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Donnelly, Raymond P
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-05-03
- Volume
- 76
- Issue
- 2
- Pages
- 314-321
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2017896938
- Cited by
- 289
- References
- 52
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 5 · 2023: 9 · 2022: 12 · 2021: 10 · 2020: 13 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 8 · 2015: 8 · 2014: 13 · 2013: 14 · 2012: 18
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (RO1 AI51139)
- National Institute of Allergy and Infectious Diseases
- American Heart Association (AHA 0245131N)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- IL-10, IL-22, IL-26, interferon lambda, IL-29, IL-28A, IL28B, cytokine-receptor complex, STAT3 signaling, STAT1, cancer cell lines, cancer targets
- MeSH terms
- Interferon gamma Receptor, Animals, Humans, Membrane Glycoproteins, Cytokines, Receptors, Interferon, Receptors, Cytokine, Receptors, Interleukin, Interleukin-10 Receptor beta Subunit
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