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

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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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RETRACTED: Suppressors of Cytokine Signaling 2 and 3 Diametrically Control Macrophage Polarization
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Background
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BackgroundInfluential
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“Therefore, SOCS1 has crucial implications for maintaining immune homeostasis, especially under pathological conditions like autoimmunity [50].”
Background
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Background
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“Suppressor of cytokine signaling 3 (SOCS3) has been proved to regulate inflammatory factors (Carow and Rottenberg 2014) and SOCS3 can regulate IL-6 signaling (Croker et al.”
Background
Dexamethasone and OLT1177 Cooperate in the Reduction of Melanoma Growth by Inhibiting STAT3 Functions
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“Socs3 encodes for an inhibitor of STAT3 that belongs to the negative feedback loop of JAK/STAT3 axis, and is the first transcript to be induced when STAT3 is active [65].”
Background
Transforming Growth Factor-β Suppresses Interleukin (IL)-2 and IL-1β Production in HIV-Tuberculosis Co-Infection
Devalraju, K. P., Neela, V. S. K., Chintala, S., Krovvidi, S. S., & Valluri, V. L. (2019) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2018.0164 · Cited by 9
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“SOCS proteins act as substrate adapters for ubiquitination and proteosomal degradation of different receptors (11).”
BackgroundSelf-citation
p73α1, a p73 C-terminal isoform, regulates tumor suppression and the inflammatory response via Notch1
Laubach, K., Yan, W., Kong, X., Sun, W., Chen, M., Zhang, J., & Chen, X. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2123202119 · Cited by 9
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“The expression of SOCS3 is decreased in the placentas of women with intrahepatic cholestasis, demonstrating its essential role in placental development (2,3).”
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“Unlike necrosis, apoptosis can have beneficial effects and be reversed by the activation of prosurvival pathways, including the Janus kinase- (JAK-) STAT signaling pathway in which cardiacspecific SOCS-3 plays a key role in promoting myocardial IR-induced injury [21].”
Background
Endogenous blocking of TLR2 along with TNF-α and IL-1β ameliorates the severity of the S. aureus arthritis via modulating STAT3/SOCS3 expressions in tissue resident macrophages
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“SOCS3 has been extensively investigated in immune cells for its role in regulating inflammation [19].”
Background
MicroRNAs Regulate Tumorigenesis by Downregulating SOCS3 Expression: An In silico Approach
Al-Asadi, S. A., Mansour, H., Ataimish, A. H., Al-Kahachi, R. E. S., & Rampurawala, J. (2023) · Bioinformatics and Biology Insights · doi:10.1177/11779322231193535 · Cited by 8
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“Furthermore, we showed an increased gene expression of SOCS3, a negative regulator of JAK/STAT3 signaling in PXEF [23], which inhibits the activity of JAK and, consequently, the activation and phosphorylation of STAT3 [42].”
Background
Stimulation of Formyl Peptide Receptor-2 by the New Agonist CMC23 Protects against Endotoxin-Induced Neuroinflammatory Response: A Study in Organotypic Hippocampal Cultures
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“Some studies have shown that the inhibition of SOCS3 can limit the function of inflammatory cytokines and affect the polarization of macrophages [29, 30].”
Background
Insights into gene expression profiles induced by Socs3 depletion in keratinocytes
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“These SOCS proteins negatively regulate the signaling pathway of hormones including leptin and insulin [71, 72].”
Background
Latent M. tuberculosis infection is associated with increased inflammatory cytokine and decreased suppressor of cytokine signalling (SOCS)‐3 in the diabetic host
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Self-citation
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Kawana, N., Yamamoto, Y., Kino, Y., & Satoh, J. (2014) · Cited by 8
Detection of differentially abundant cell subpopulations discriminates biological states in scRNA-seq dataPreprint
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“…the level in LL (log 2 FC = 2.96, adj. p = 0.0003), followed by SOCS3 (log 2 FC = 2.05, adj. p = 0.001), a master regulator of the immune response (42), and FCGR1A (log 2 FC = 1.97, adj. p = 0.003) and FCGR1B (log 2 FC = 1.90, adj. p = 0.003), encoding the Fc gamma receptors 1A (CD64A) and 1B…”
BackgroundInfluential
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Liang, T., Zhang, Z., Bai, Z., Xu, L., & Xu, W. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25169007 · Cited by 7
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“In the URT, SOCS3 was upregulated in all ferrets and has been shown to down-modulate IFN signaling in a RIG-I-dependent pathway to inhibit antiviral responses and suppress the in ﬂ ammatory response 54 – 56 .”
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“[6] As accumulation of phytosterols (PS) in the liver (from the i.v. lipid emulsion) during PNAC interferes with FXR signaling and bile-transporter expression,[23] we next examined the interaction between PS, STAT3, and FXR signaling. siRNA knockdown of STAT3 in HepG2 or Huh7 cells significantly reduced STAT3 mRNA lev…”
MethodInfluential
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“Through this mechanism, SOCS3 participates in controlling various cellular functions, including cell growth, differentiation, migration, and inflammatory responses (45, 46).”
Background
RETRACTED: Essential blood molecular signature for progression of sepsis-induced acute lung injury: Integrated bioinformatic, single-cell RNA Seq and machine learning analysis
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Retracted
The role of suppressor of cytokine signaling 3 in inflammatory bowel disease and its associated colorectal cancer
Zhang, P., Pei, B., Yi, C., Akanyibah, F. A., & Mao, F. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167578 · Cited by 7
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“4 * * SOCS3 PPARγ target gene, negative regulator via JAK/STAT [80] −2.”
Effects of potentially functional polymorphisms in suppressor of cytokine signaling 3 ( SOCS 3) on the risk of head and neck squamous cancer
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[Retracted] SOCS3 Gene Polymorphism and Hypertension Susceptibility in Chinese Population: A Two‐Center Case‐Control Study
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“And it has been shown to be involved in regulating signal transduction through a variety of cytokines, including insulin signaling and leptin signaling Carow & Rottenberg [7].”
Background
Retracted
TNF deficiency dysregulates inflammatory cytokine production leading to lung pathology and death during respiratory poxvirus infectionPreprint
Kels, M. J. T., Ng, E., Rumaih, Z. A., Pandey, P., Ruuls, S. R., Körner, H., Newsome, T. P., Chaudhri, G., & Karupiah, G. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.22.883728 · Cited by 7
“It is likely that the combined actions of increased levels of PIAS3 and SOCS3 in the anti-IL-6-treated mice contributed to dampening of STAT3 activation and to effective amelioration of lung pathology and survival of mice.”
BackgroundInfluential
Filgotinib Improves Experimental Pulmonary Fibrosis by Modulating JAK1/STAT3/SOCS3/IL‐17A Signalling
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Epigenetic biomarkers of socioeconomic status are associated with age-related chronic diseases and mortality in older adults
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“Both inflammation and infection can stimulate the expression of SOCS3 in different cell populations (72). cg18181703 was also identified in prior EWAS of educational attainment and social disadvantage (4, 73).”
17β-Trenbolone Increases the Release of Lipocalin 2 via the Brain–Liver Axis and Causes Alzheimer’s Disease-Like Symptoms in CSDS-Induced Mice
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“Socs3 binds to JAK kinase to inhibit further Stat3 activation, thereby maintaining signaling balance [81].”
STAT3 induced BRD9 activation promotes intrahepatic cholangiocarcinoma progression by enhancing CD36 controlled fatty acid metabolism
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Screening for anti-influenza virus compounds from traditional Mongolian medicine by GFP-based reporter virus
Nie, M., Li, X., Zhang, S., Zeng, D., Cai, Y., Peng, D., Jiang, T., Shi, J.-P., & Li, J. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1431979 · Cited by 6
“Analysis of the expression changes of genes in key signaling pathway indicated that it could upregulate the expression of certain genes related to immunity, such as IRF3 (Al and Brady, 2022), SOCS3 (Carow and Rottenberg, 2014), and IL32 (Zhu et al., 2022) (Figure 5C).”
Background
In vitro HIV DNA integration in STAT3 drives T cell persistence—A model of HIV-associated T cell lymphoma
Rist, M., Kaku, M., & Coffin, J. M. (2025) · PLoS Pathogens · doi:10.1371/journal.ppat.1013087 · Cited by 6
“Additionally, downstream targets of STAT3, such as SOCS3 [59,60] and SGK1 [61], were also upregulated (Fig 3D).”
Socs3 ablation in kisspeptin cells partially prevents lipopolysaccharide-induced body weight loss
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Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection, and reproduction in a wild rodent
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“151 Both Il33 and Socs3 also share an association with the inflammatory response [26,27].”
Background
Posing the rationale for synthetic lipoxin mimetics as an adjuvant treatment to gold standard atherosclerosis therapies
Millar, B., & de Gaetano, M. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1125858 · Cited by 7
“SOCS3 inhibits macrophage-mediated Th1 activation and the subsequent release of pro-inflammatory cytokines IL-1, IL-6, TNF-α, and MMPs (Carow and Rottenberg, 2014).”
BackgroundInfluential
AAV-BDNF gene therapy ameliorates a hypothalamic neuroinflammatory signature in the Magel2-null model of Prader-Willi syndrome
Queen, N. J., Huang, W., Zou, X., Mo, X. M., & Cao, L. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.09.004 · Cited by 7
TGF-β Promotes the Postselection Thymic Development and Peripheral Function of IFN-γ–Producing Invariant NKT cells
Morgan, R. C., Frank, C., Greger, M., Attaway, M., Sigvardsson, M., Bartom, E. T., & Kee, B. L. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2200809 · Cited by 6
Advances in clinical outcomes: What we have learned during the COVID-19 pandemic
Al-Musa, A., LaBere, B., Habiballah, S. B., Nguyen, A. A., & Chou, J. S. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.12.775 · Cited by 6
“It inhibits antigen presentation and proinflammatory cytokine secretion from monocytes and dendritic cells by reducing MHC class II expression and restrains T-cell activation,(87,88) in part through upregulating expression of the suppressor of cytokine signaling protein 3, which inhibits CD8(1) T-cell proliferation.(8…”
Background
Fetal anemia and elevated hepcidin in a mouse model of fetal alcohol spectrum disorder
Helfrich, K. K., Saini, N., Kwan, S. T., Rivera, O. C., Mooney, S. M., & Smith, S. M. (2023) · Pediatric Research · doi:10.1038/s41390-023-02469-6 · Cited by 6
Exploring and Validating the Mechanism of Ulinastatin in the Treatment of Sepsis-Associated Encephalopathy Based on Transcriptome Sequencing
Hu, W., Zhang, X., Wu, Z., Luo, Y., Hu, B., & Zou, X. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s488400 · Cited by 5
“48 Li et al suggested that SOCS3 could serve as a diagnostic and therapeutic target for SAE and hepatic encephalopathy due to its association with immune cells, further supporting our research conclusions.”
β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males
Pilipović, I., Stojić-Vukanić, Z., Prijić, I., Jasnic, N. I., Djordjevic, J. D., & Leposavić, G. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01246-z · Cited by 5
“2013; Carow and Rottenberg, 2014).”
Downregulated miR-15b-5p induces suppressor of cytokine signaling 6 (SOCS6) expression during viral hemorrhagic septicemia virus infection in olive flounder (Paralichthys olivaceus)
Lee, Y. J., Park, E. G., Kim, W. R., Bae, W. H., Lee, D. H., Lee, Y., Kim, D.-H., Choi, Y. H., Cha, H., Kim, S., et al. (2022) · Aquaculture · doi:10.1016/j.aquaculture.2022.738811 · Cited by 5
Epigenome-Wide Association Study of Biomarkers of Liver Function Identifies Albumin-Associated DNA Methylation Sites Among Male Veterans with HIV
Titanji, B. K., Lee, M., Wang, Z., Chen, J., Hui, Q., Re, V. L., So‐Armah, K., Justice, A. C., Xu, K., Freiberg, M. S., et al. (2022) · Frontiers in Genetics · doi:10.2139/ssrn.4149559 · Cited by 6
Multi-Omic Profiles in Infants at Risk for Food Reactions
Beheshti, R., Stone, S., Chandran, D., & Hicks, S. D. (2022) · Genes · doi:10.3390/genes13112024 · Cited by 5
“Notably, IL-6, a putative inflammatory mediator in atopy, is also a potent activator of the JAK-STAT pathway [29–31], which has been implicated in atopy and airway hyper-reactivity [32,33].”
Background
Early growth response 2, a novel target of pelvic organ prolapse, is highly expressed in anterior vaginal wall tissues with pelvic organ prolapse
Jin, X., Xu, H., Hu, Q., Yin, Y., Qin, M., & Xia, Z. (2023) · Histochemistry and Cell Biology · doi:10.1007/s00418-023-02240-2 · Cited by 5
“Among the SOCS protein family, SOCS3 is an important member and a cytokine-induced negative regulator of cytokine signaling pathways (Carow and Rottenberg 2014).”
Stat3 Regulates Developmental Hematopoiesis and Impacts Myeloid Cell Function via Canonical and Non-Canonical Modalities
Sobah, M. L., Liongue, C., & Ward, A. C. (2024) · Journal of Innate Immunity · doi:10.1159/000538364 · Cited by 4
“In addition, germline STAT3 mutations – presumed to be LOF – have been linked to the development of autoimmunity and impaired innate immunity leading to enhanced susceptibility to infection [10, 72].”
Background
Utilizing Nanopore direct RNA sequencing of blood from patients with sepsis for discovery of co- and post-transcriptional disease biomarkers
He, J., Ganesamoorthy, D., Chang, J. J. ‐., Zhang, J., Trevor, S. L., GIBBONS, K. S., McPherson, S. J., Kling, J. C., Schlapbach, L. J., Blumenthal, A., et al. (2025) · BMC Infectious Diseases · doi:10.1186/s12879-025-11078-z · Cited by 8
“Most genes in the first peak are actively involved in inflammatory processes and immune response, including CD36 [49] , SOCS3 [50] , TNFRSF1A [51] , STAT3 [52] , PTEN [53], and PRKCB [54].”
Heat Shock Factor 1 Inhibits the Expression of Suppressor of Cytokine Signaling 3 in Cerulein-Induced Acute Pancreatitis
Wang, G., Xiao, G., Hai, L., Chen, G., Wang, X., Wen, P., Li, T., Wen, J., & Xiao, X. (2017) · Shock · doi:10.1097/shk.0000000000001071 · Cited by 5
Association of Aberrant Promoter Methylation Changes in the Suppressor of Cytokine Signaling 3 (SOCS3) Gene with Susceptibility to Crohn's Disease
Sanati, G., Jafari, D., Noruzinia, M., Daryani, N. E., Ahmadvand, M., Teimourian, S., & Rezaei, N. (2022) · Avicenna Journal of Medical Biotechnology · doi:10.18502/ajmb.v14i2.8887 · Cited by 5
“The suppressors of cytokine signaling (SOCS) 3 protein as a member of SOCS family is the key physiological regulators of cytokine-mediated activation of STAT3 by inhibiting the catalytic activity of JACKs 11 .”
Background
Exploring the molecular underpinning of psoriasis and its associated comorbidities through network approach: cross talks of genes and pathways
Choudhary, S., Khan, N. S., Verma, R., Saxena, P., Singh, H., Jain, A. K., Thomas, G., Pradhan, D., & Kumar, N. (2023) · 3 Biotech · doi:10.1007/s13205-023-03533-y · Cited by 5
“It’s role in both the disease can be associated to its mechanism of cytokine regulation and inhibiting STAT3 activation which also has a role in cellular pathway (Carow and Rottenberg 2014).”
Background
Involvement of orexin in lipid accumulation in the liver
Mochizuki, A., Nakayama, K., Nakamura, S., Dantsuji, M., Kamijo, R., Shioda, S., Sakurai, T., Ozeki, M., & Inoue, T. (2018) · Journal of Oral Biosciences · doi:10.1016/j.job.2018.07.001 · Cited by 5
SOCS3 overexpression in T cells ameliorates chronic airway obstruction in a murine heterotopic tracheal transplantation model
Mesaki, K., Yamane, M., Sugimoto, S., Fujisawa, M., Yoshimura, T., Kurosaki, T., Otani, S., Miyoshi, S., Oto, T., Matsukawa, A., et al. (2019) · Surgery Today · doi:10.1007/s00595-018-1753-5 · Cited by 5
Lack of association between SOCS3 and SOCS7 polymorphisms and psoriasis
Özçep, M., Atsü, N., Tekin, N. S., & Çelik, S. (2022) · Immunity Inflammation and Disease · doi:10.1002/iid3.695 · Cited by 5
“The SOCS family of proteins are cytokine‐inducible inhibitors of the JAK–STAT signaling pathways.(16) Sonkoly et al.”
Background
Suppressor of Cytokine Signaling 3 Derived Peptide as a Therapeutic for Inflammatory, and Oxidative Stress Induced Damage to the RetinaPreprint
Ahmed, C. M. I., Patel, A. P., Johnson, H. M., Ildefonso, C. J., & Lewin, A. S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.04.556227 · Cited by 5
“Several studies have shown that SOCS3 inhibits choroidal neovascularization [ 56 –59] and controls infection and inflammation [ 60 , 61 ].”
Background
Bilirubin Alleviates Spinal Cord Injury by Enhancing SOCS3 ‐Mediated Anti‐Inflammatory Effects via Gas6‐Axl Signaling
Jiang, K., Luan, Y., Shen, N., Qi, X., Hu, L., Wang, Y., Liu, W., Wang, R., Lin, T., & Peng, D. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70538 · Cited by 5
Hypervolemia in Dialysis Patients Impairs STAT3 Signaling and Upregulates miR-142-3p: Effects on IL-10 and IL-6
Ulrich, C., Fiedler, R., Herberger, E., Canim, Z., Markau, S., & Girndt, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073719 · Cited by 4
“Other study groups state that SOCS3 lacks affinity to the IL-10 receptor and thus has no effect on IL-10 signaling [36,37].”
Background
A single amino acid in the Salmonella effector SarA/SteE triggers supraphysiological activation of STAT3 for anti-inflammatory gene expression
Gaggioli, M. R., Jones, A. G., Panagi, I., Washington, E., Loney, R. E., Muench, J. H., Foster, M. W., Brennan, R. G., Thurston, T. L. M., & Ko, D. C. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115530 · Cited by 5
Luciferase Reporter Mice for In Vivo Monitoring and Ex Vivo Assessment of Hypothalamic Signaling of Socs3 Expression
Cordonier, E. L., Liu, T., Saito, K., Chen, S. S., Xu, Y., & Fukuda, M. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00077 · Cited by 4
“Induced SOCS3 inhibits cytokine signaling via the inhibition of JAK activity and targets the receptor complex for proteasomal degradation [4].”
Background
Inflammatory Pre-Conditioning of Adipose-Derived Stem Cells with Cerebrospinal Fluid from Traumatic Brain Injury Patients Alters the Immunomodulatory Potential of ADSC Secretomes
Üçal, M., Maurer, C., Etschmaier, V., Hamberger, D., Grünbacher, G., Tögl, L., Roosen, M. J., Molčányi, M., Vorholt, D., Hatay, F. F., et al. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2020.7017 · Cited by 4
“46 Whereas the JAK-STAT pathway is known for the production of inﬂam-matory cytokines, their inhibition could result in reduction of macrophage IL-10 production given that IL-10 also exerts its anti-inﬂammatory effects through the same pathway.”
A Review on the Dual Role of SOCS3 in Cancer
Chakraborty, R., Darido, C., Alnakli, A., Hu, H., & Vickery, K. (2022) · Research in Oncology · doi:10.21608/resoncol.2022.114548.1159 · Cited by 4
Nanosphere pharmacodynamics improves safety of immunostimulatory cytokine therapy
Lacinski, R. A., Dziadowicz, S. A., Stewart, A., Chaharbakhshi, E. O., Akhter, H., Pisquiy, J. J., Victory, J. H., Hardham, J. B., Chew, C., Prorock, A. J., et al. (2024) · iScience · doi:10.1016/j.isci.2024.108836 · Cited by 4
“Upregulation of SOCS3, an integral regulator responsible for maintaining controlled inﬂammation downstream of both pro-inﬂammatory STAT1/STAT3 (IL-6) and STAT4 (IL-12) signal transduction, 71,72 suggests healthy inﬂammatory signaling with IL12ns dosing.”
IL-17A produced by POMC neurons regulates diet-induced obesity
Gallo, R., Teijeiro, A., Angulo-Aguado, M., & Djouder, N. (2024) · iScience · doi:10.1016/j.isci.2024.110259 · Cited by 4
Inflammatory Intracellular Signaling in Neurons Is Influenced by Glial Soluble Factors in iPSC-Based Cell Model of PARK2-Associated Parkinson’s Disease
Gerasimova, T., Poberezhniy, D., Nenasheva, V. V., Stepanenko, E. A., Arsenyeva, E. L., Novosadova, L. V., Grivennikov, I. A., Illarioshkin, S. N., Lagarkova, M. A., Tarantul, V. Z., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179621 · Cited by 4
“Regulates a STAT3-mediated chemokine and chemokine receptor function, causes degradation of p65 NF-κ B [35,36].”
Background
The investigation of SNP in SOCS2 gene and its effect on milk yield, fat, protein, and somatic cell count in Awassi ewes
Hasan, M. U., & Ceyhan, A. (2024) · Tropical Animal Health and Production · doi:10.1007/s11250-024-04147-z · Cited by 4
“Furthermore, the milk characters milk yield, fat, protein, total solids were analyzed to study the effect of SCC on milk yield, fat, protein and total solids.”
Inhibitory DNA Aptamer Tools against SOCS3-gp130 Interactions
Zhang, X., Hou, Y., Chen, W., Fu, T., Wei, Y., & Tan, W. (2024) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c09252 · Cited by 4
Eosinophilic Fasciitis and Morphea Share Gene Signatures of Inflammatory Cell Death, Self-DNA Recognition, and Enhanced Jak/Signal Transducer and Activator of Transcription Signaling
Crisler, W. J., Rowley, R., Oke, O. H., Steuart, S. J., Modi, M. M., Davis, D. L., Chen, C., Gray, L., Teague, J. E., Zhan, Q., et al. (2025) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2025.05.023 · Cited by 6
Factors regulating Th17 cells: a review
Seki, R., & Nishizawa, K. (2016) · Biomedical Research and Clinical Practice · doi:10.15761/brcp.1000122 · Cited by 4
The role of interleukin-24 in atopic dermatitis
Vu, Y. H., Furue, M., & Tsuji, G. (2021) · Exploration of Immunology · doi:10.37349/ei.2021.00002 · Cited by 5
“Suppressor of cytokine signaling-3 (SOCS3) inhibited JAK1, JAK2, and tyrosine protein kinase 2 but not JAK3, and it downregulated STAT3 activation [47].”
Background
Identification of Critical Genes and Signaling Pathways in Human Monocytes Following High-Intensity Exercise
Li, P., & Luo, L. (2021) · Healthcare · doi:10.3390/healthcare9060618 · Cited by 4
“negative regulator of inflammation by suppressing STAT3 activation [41].”
Background
Maternal Socs3 knockdown attenuates postnatal obesity caused by an early life environment of maternal obesity and intrauterine overnutrition in progeny mice
Zhu, F. Y., Zhang, D., Shen, F., Xu, K., Huang, X. S., Liu, J., Zhang, J., & Teng, Y. (2021) · IUBMB Life · doi:10.1002/iub.2526 · Cited by 4
Combined Bacterial Antigen Lipopolysaccharide and Lipoteichoic Acid Increase Cal 27 Oral Cancer Cell Proliferation
Ranganathan, S., Chakraborty, R., Hu, H., Mangani, A. S., Vickery, K., & Ranganathan, S. (2021) · Dental Oral Biology and Craniofacial Research · doi:10.31487/j.dobcr.2021.01.03 · Cited by 4
“This may be because of the lower expression of SOCS3, which has been reported to have a positive feedback loop with STAT3 for Cal 27 [18].”
Background
A common human missense mutation of vesicle coat protein SEC23B leads to growth restriction and chronic pancreatitis in mice
Wei, W., Liu, Z., Zhang, C., Khoriaty, R. N., Zhu, M., & Zhang, B. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101536 · Cited by 4
“SOCS3 is a major mediator of inflammation-induced GH resistance in liver (44, 50, 52).”
Background
Thiazoline-related TRPA1 agonist odorants orchestrate survival fate in micePreprint
Matsuo, T., Isosaka, T., Tang, L., Soga, T., Kobayakawa, R., & Kobayakawa, K. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.17.100933 · Cited by 4
“…of Nfkbia and Nfkbiz which suppress NFκb activity, a major protein involved in cytokine production and inflammatory responses (Hayden and Ghosh, 2012), as well as Socs3, which suppresses cytokine signaling (Carow and Rottenberg, 2014), in multiple subpopulations including monocytes and DCs.”
Background
A consensus single-cell transcriptomic atlas of dermal fibroblast heterogeneityPreprint
Ascensión, A. M., & Izeta, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.05.611379 · Cited by 4
Individuals with latent tuberculosis in a high TB endemic country show mild COVID-19
Abbas, U., Masood, K. I., Iqbal, T., Jamil, B., Qaiser, S., Yameen, M., Rottenberg, M., Hussain, R., & Hasan, Z. (2025) · PLoS ONE · doi:10.1371/journal.pone.0339240 · Cited by 3
Self-citation
Transcriptomic Analysis of THP-1 Cells Exposed by Monosodium Urate Reveals Key Genes Involved in Gout
Wang, G., Liu, Z., Zheng, Y., Sheng, C., Hou, X., Yao, M., Zong, Q., Tang, D., Zhou, Z., Zhang, T., et al. (2023) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/0113862073262471231011043339 · Cited by 3
Transcriptome analysis of skeletal muscle in dermatomyositis, polymyositis, and dysferlinopathy, using a bioinformatics approach
Jeong, H.-N., Lee, T. G., Park, H. J., Yang, Y. D., Oh, S., Kang, S., & Choi, Y. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1328547 · Cited by 3
Wound healing potential and anti-inflammatory action of extracts and compounds of Myrciaria plinioides D. Legrand leaves
Marmitt, D. J., Vettorazzi, G., Bortoluzzi, L. D., Alves, C., Silva, J., Pintéus, S., Martins, A., Gaspar, H., Pedrosa, R., da Silva, J., et al. (2024) · Inflammopharmacology · doi:10.1007/s10787-024-01547-3 · Cited by 3
“…and inducing STAT3 (Signal Transducer and Activator of Transcription-3)—induces the synthesis of SOCS3 (cytokine-3 signal suppressor), one of the genes responsive to IL-10, which is one important regulator of inflammation (Carow and Rottenberg 2014), blocking the phosphorylation of MAPKs (Fig.”
Elevated Plasma IL-6 Coincides with Activation of STAT3 in PBMC After Acute Resistance Exercise
Tsai, S., Cheng, H.-C., Little, J. P., Islam, H., & Liu, H. (2024) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003503 · Cited by 3
Possible Anti-Aging and Anti-Stress Effects of Long-Term Transcendental Meditation Practice: Differences in Gene Expression, EEG Correlates of Cognitive Function, and Hair Steroids
Wenuganen, S., Walton, K. G., Travis, F. T., Tobias Stalder, A., Wallace, R. K., Srivastava, M., & Fagan, J. B. (2025) · Biomolecules · doi:10.3390/biom15030317 · Cited by 3
“SOCS3 plays a major role in regulating inflammation and infections [62,63].”
Diabetes exacerbates SARS-CoV-2 replication through ineffective pulmonary interferon responses, delayed cell-mediated immunity, and disruption of leptin signaling
Thieulent, C., Balasuriya, U. B. R., Tseng, A. E., Crossland, N. A., Stephens, J. M., Dittmar, W., Staszkiewicz, J., Richt, J. A., & Carossino, M. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1513687 · Cited by 4
“Interestingly, both SOCS3 and STAT3 can negatively regulate type I interferon (IFN) responses, with the latter suppressing STAT1 through its sequestration (Ho and Ivashkiv, 2006; Carow and Rottenberg, 2014; Wang et al., 2019).”

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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