SOCS proteins, cytokine signalling and immune regulation
Open accessAbstract
Suppressor of cytokine signalling (SOCS) proteins are inhibitors of cytokine signalling pathways. Studies have shown that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules positively and negatively regulate macrophage and dendritic-cell activation and are essential for T-cell development and differentiation. Evidence is also emerging of the involvement of SOCS proteins in diseases of the immune system. In this Review we bring together data from recent studies on SOCS proteins and their role in immunity, and propose a cohesive model of how cytokine signalling regulates immune-cell function.
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IL-6 elicits a pro-inflammatory response, while IL-10 signaling leads to an anti-inflammatory response, despite both receptors activating STAT3.
“The reason why IL-6 induces a pro-inflammatory response, while IL-10 induces an anti-inflammatory response, despite both cytokines activating the same transcription factor, STAT3, is not well understood.”
From A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs (2012) · cites this paper as [10]
IL-6 induces a transient STAT3 signal, while IL-10 induces a sustained STAT3 signal.
“This leads to IL-6 inducing a transient STAT3 signal, while IL-10 induces a sustained STAT3 signal [10].”
From A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs (2012) · cites this paper as [10]
SOCS3 induced by STAT3 can bind to the IL-6 receptor but cannot bind to the IL-10 receptor.
“One key distinction between the two pathways is that the inhibitor, suppressor of cytokine signaling 3 (SOCS3) induced by STAT3, can bind to the IL-6 receptor, but cannot bind to the IL-10 receptor.”
From A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs (2012) · cites this paper as [10]
The model is consistent with Yoshimura's proposal that sustained STAT3 signals are essential for anti-inflammatory responses while transient signals promote inflammation.
“Yoshimura [10] has proposed that sustained STAT3 signals are essential for anti-inflammatory responses while transient signals promote inflammation, which is consistent with our model.”
From A Model for How Signal Duration Can Determine Distinct Outcomes of Gene Transcription Programs (2012) · cites this paper as [10]
SOCS3 mRNA is rapidly induced by activated STAT3 and STAT1; SOCS3 protein interacts with the pYSTV motif of gp130 through its SH2 domain and inhibits JAK activity through its kinase-inhibitory region, restricting further STAT3 activation.
“Another inhibitory loop is mediated by suppressor of cytokine signaling (SOCS)3 (Yoshimura et al., 2007). SOCS3 mRNA is rapidly induced by activated STAT3 and STAT1, and SOCS3 protein interacts with pYSTV motif of gp130 through its SH2 domain and inhibits JAK activity through its kinase-inhibitory region, thereby restricting further STAT3 activation (Babon et al., 2012; Kershaw et al., 2013).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Yoshimura et al., 2007
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- Authors
- Yoshimura, A., Naka, T., & Kubo, M.
- Affiliations
- Kyushu University (JP)
- National Institute of Biomedical Innovation (JP)
- RIKEN (JP)
- Corresponding author
- Yoshimura, Akihiko
- Venue
- Nature Reviews Immunology
- Published
- 2007-05-18
- Volume
- 7
- Issue
- 6
- Pages
- 454-465
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2093442991
- Cited by
- 1,580
- References
- 7
- Citations by year
- 2026: 44 · 2025: 66 · 2024: 66 · 2023: 71 · 2022: 72 · 2021: 92 · 2020: 82 · 2019: 82 · 2018: 91 · 2017: 96 · 2016: 70 · 2015: 91 · 2014: 112 · 2013: 89 · 2012: 110
- FWCI
- 8.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature reviews. Immunology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- suppressor of cytokine signaling, cytokine signaling, immune regulation, innate immunity, adaptive immunity, macrophage activation, dendritic cell activation, T cell development, immune-related diseases
- MeSH terms
- Animals, Cell Differentiation, Dendritic Cells, Humans, Macrophage Activation, Macrophages, Models, Biological, T-Lymphocytes, Signal Transduction, Cytokines, Suppressor of Cytokine Signaling Proteins
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