Cited by 566Cytokine Signaling Pathways and InteractionsAdipokines, Inflammation, and Metabolic DiseasesProtein Tyrosine Phosphatases

The DOI matches its Crossref record; 178 of the 179 references it cites were found in a registry or an index.

SOCS3, a Major Regulator of Infection and Inflammation

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Carow, Berit, Rottenberg, Martin E.·2014·Frontiers in Immunology

DOI 10.3389/fimmu.2014.00058PMC PMC3928676

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Abstract

In this review, we describe the role of suppressor of cytokine signaling-3 (SOCS3) in modulating the outcome of infections and autoimmune diseases as well as the underlying mechanisms. SOCS3 regulates cytokine or hormone signaling usually preventing, but in some cases aggravating, a variety of diseases. A main role of SOCS3 results from its binding to both the JAK kinase and the cytokine receptor, which results in the inhibition of STAT3 activation. Available data also indicate that SOCS3 can regulate signaling via other STATs than STAT3 and also controls cellular pathways unrelated to STAT activation. SOCS3 might either act directly by hampering JAK activation or by mediating the ubiquitination and subsequent proteasome degradation of the cytokine/growth factor/hormone receptor. Inflammation and infection stimulate SOCS3 expression in different myeloid and lymphoid cell populations as well as in diverse non-hematopoietic cells. The accumulated data suggest a relevant program coordinated by SOCS3 in different cell populations, devoted to the control of immune homeostasis in physiological and pathological conditions such as infection and autoimmunity.

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Figure 1 Simultaneous binding of SOCS3 to JAK and the gp130 cytokine receptor. Adapted from Ref. (56).CC BY · PubMed Central

Figure 2 Role of SOCS3 in the control of infection. (A) During M. tuberculosis and T. gondii infection, SOCS3 is induced in macrophages and DCs prevents the IL-6-mediated inhibition of IL-12 secretion, promoting a CD4+ cell-dependent IFN-γ expression. (B) SOCS3 controls the development of γδ+ T cells. Such control is critical for proper protection against M. tuberculosis.CC BY · PubMed Central

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1 retracted

RETRACTED: Suppressors of Cytokine Signaling 2 and 3 Diametrically Control Macrophage Polarization
Spence, S., Fitzsimons, A., Boyd, C. R., Kessler, J., Fitzgerald, D. C., Elliott, J., Gabhann, J. N., Smith, S., Sica, A., Hams, E., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.09.013 · Cited by 96
Retracted
Yaşlı Kadınlarda Üreme Sağlığı
Kokanalı, D., & Engin Üstün, Y. (n.d.) · DergiPark (Istanbul University) · Cited by 170,090
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Background
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“SOCS3 has been also suggested to inhibit IL-12-induced STAT4 activation by direct binding to IL-12Rβ2 (37), the IL-12R subunit that is not shared with the IL-23R.”
BackgroundInfluential
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Additional file 3 of Deletion of Socs3 in LysM+ cells and Cx3cr1 resulted in age-dependent development of retinal microgliopathy
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Additional file 2 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
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Additional file 5 of Deletion of Socs3 in LysM+ cells and Cx3cr1 resulted in age-dependent development of retinal microgliopathy
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Additional file 11 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
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Additional file 7 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
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Additional file 10 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
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Additional file 8 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
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Additional file 2 of Deletion of Socs3 in LysM+ cells and Cx3cr1 resulted in age-dependent development of retinal microgliopathy
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Additional file 4 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
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Additional file 6 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
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Additional file 3 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
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Additional file 5 of Genome wide DNA methylation analysis of alveolar capillary dysplasia lung tissue reveals aberrant methylation of genes involved in development including the FOXF1 locus
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Additional file 5 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
Olney, K. C., de Ávila, C., Todd, K. T., Tallant, L. E., Barnett, J. H., Gibson, K. A., Hota, P., Pandian, A. S., Durgun, P. C., Serhan, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26660675
Additional file 9 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
Olney, K. C., de Ávila, C., Todd, K. T., Tallant, L. E., Barnett, J. H., Gibson, K. A., Hota, P., Pandian, A. S., Durgun, P. C., Serhan, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26660687
Additional file 6 of Deletion of Socs3 in LysM+ cells and Cx3cr1 resulted in age-dependent development of retinal microgliopathy
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Additional file 12 of Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia
Olney, K. C., de Ávila, C., Todd, K. T., Tallant, L. E., Barnett, J. H., Gibson, K. A., Hota, P., Pandian, A. S., Durgun, P. C., Serhan, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26660696
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Wang, J., Hou, G., Song, Z., Gao, K., Wang, H., & Li, T. (2026) · Journal of Cell Communication and Signaling · doi:10.1002/ccs3.70041
“17,20 In gliomas, reduced SOCS3 expression may lead to persistent STAT3 activation, thereby enhancing GSCs' survival and proliferative capabilities.”
SwitchClass distinguishes baseline- and perturbation-aligned features across intermediate molecular states
Xiao, D., Long, S., & Yang, P. (2026) · Cell Reports Methods · doi:10.1016/j.crmeth.2026.101547
Piper nigrum L. and its main component piperine ameliorate hyperuricemia and hyperuricemia-related renal inflammation through suppressing the JAK2-STAT3-XDH/SOCS3/TNF-α signalling pathway
Li, N.-C., Xin, M.-L., Song, X., Wang, H.-Y., Yang, F.-Y., Li, J.-D., & Sun, W.-L. (2026) · Food & medicine homology. · doi:10.26599/fmh.2027.9420159
Tear MicroRNA-Based Molecular Signature for Keratoconus Stratification: A Cross-Cohort Integration Study
Chang, S.-H., Hung, K. H., Tsai, H.-F., Ma, C., Hu, K., & Yeh, L. (2026) · Bioinformatics and Biology Insights · doi:10.1177/11779322261489962
“41 Although direct mechanistic confirmation in corneal tissue remains limited, these components collectively suggest a coordinated inflammatory signaling environment associated with disease activity.”
Immunometabolic network of childhood common obesity: multi-organ comorbidities mediated by gut microbiota-immune axis
Zhang, Y., Liu, P., Peng, Y., Chen, Y., Lei, E., & Liu, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1963905
BindingDB Entry 50010601: Chimeric Peptidomimetics of SOCS 3 Able to Interact with JAK2 as Anti-inflammatory Compounds.
BindingDB (2021) · UC San Diego · doi:10.7270/q2bz69k0

Authors: Carow, B., & Rottenberg, M. E.
Affiliations: Karolinska Institutet (SE)
Corresponding author: Carow, Berit
ORCID: Carow, Berit
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2014
Volume: 5
Pages: 58-58
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2014.00058
PMC: PMC3928676
OpenAlex: W2140013858
Cited by: 555
References: 179
Citations by year: 2026: 31 · 2025: 55 · 2024: 65 · 2023: 71 · 2022: 64 · 2021: 58 · 2020: 43 · 2019: 52 · 2018: 31 · 2017: 25 · 2016: 27 · 2015: 24 · 2014: 9
FWCI: 3.22
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Immunology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: SOCS3, suppressor of cytokine signaling, infection, inflammation, autoimmune disease, STAT3 activation, JAK kinases, cytokine signaling, receptor ubiquitination, proteasomal degradation, immune homeostasis, myeloid cells, lymphoid cells

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SOCS3, a Major Regulator of Infection and Inflammation

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