Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function

Palmer, Douglas C.; Restifo, Nicholas P.

doi:10.1016/j.it.2009.09.009

Cited by 241 publications

(221 citation statements)

References 156 publications

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“…This study was not designed to elucidate the factors responsible for enhanced SOCS-3 expression, but IL-1␤ was able to enhance SOCS-3 expression in all patient groups. We previously demonstrated that joint inflammation causes rapid up-regulation of SOCS-3 protein in murine artic- (12,26,27). Among the various cytokines, IL-10 is a likely candidate responsible for high SOCS-3 levels.…”

Section: Discussionmentioning

confidence: 99%

Enhanced suppressor of cytokine signaling 3 in arthritic cartilage dysregulates human chondrocyte function

Loo¹,

Veenbergen²,

Brand³

et al. 2012

Arthritis & Rheumatism

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Objective. To determine the expression of suppressor of cytokine signaling 3 (SOCS-3) in human articular chondrocytes and its functional consequences.Methods. Chondrocytes were isolated from the cartilage of patients with osteoarthritis (OA), patients with rheumatoid arthritis (RA), and trauma patients and from the healthy cartilage of patients with a femoral neck fracture. The human chondrocyte cell line G6 and primary bovine chondrocytes were used in validation experiments. SOCS-3 messenger RNA (mRNA) expression was measured by quantitative polymerase chain reaction, and SOCS-3 protein levels were determined by Western blotting and immunohistochemical analysis. Conclusion. This study demonstrated that both SOCS-3 mRNA and SOCS-3 protein are expressed in human arthritic chondrocytes and affect cellular responses involved in cartilage pathology.

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Section: Discussionmentioning

confidence: 99%

Enhanced suppressor of cytokine signaling 3 in arthritic cartilage dysregulates human chondrocyte function

Loo¹,

Veenbergen²,

Brand³

et al. 2012

Arthritis & Rheumatism

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“…However, the detailed mechanism has to be elaborated in further studies. SH2-independent recruitment of STAT3 might serve to avoid negative feedback by proteins such as suppressor of cytokine signaling 3 (SOCS3), which can compete with STAT factors for phosphotyrosines (46). IL-6-gp130-STAT3 activation is rapidly switched off by SOCS3-negative feedback regulation (47).…”

Section: Discussionmentioning

confidence: 99%

Identification of Canonical Tyrosine-dependent and Non-canonical Tyrosine-independent STAT3 Activation Sites in the Intracellular Domain of the Interleukin 23 Receptor

Floß

Mrotzek

Klöcker

et al. 2013

Journal of Biological Chemistry

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Background: Activation of STAT3 is the major signaling pathway of IL-23. Results:The study provides detailed characterization of IL-23-dependent signal transduction with the focus on STAT3 phosphorylation. Conclusion: Canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites are located within the IL-23R. Significance: This may be the first step in elucidating the signal transduction of IL-23, an important cytokine for T H 17 cell development.

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“…Genes upregulated by ILT3Fc, which are predicted to be targeted by miR-30b and miR146a, are BCL6 and CXCR4, respectively. There is already evidence that miR-146a controls expression of CXCR4 (29), miR-21 controls TGFBR2 (30), and miR-155 acts on SOCS1, a negative regulator of cytokine signaling through STAT1 (31)(32)(33). SOCS1 also contains a putative target site for miR-30b.…”

Section: Induction Of Bcl6 Socs1 and Dusp10 By Ilt3fc Is 39-utr Depmentioning

confidence: 99%

Downregulation of Inflammatory MicroRNAs by Ig-like Transcript 3 Is Essential for the Differentiation of Human CD8+ T Suppressor Cells

Chang

Zhang

Liu

et al. 2012

The Journal of Immunology

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We have investigated the mechanism underlying the immunoregulatory function of membrane Ig-like transcript 3 (ILT3) and soluble ILT3Fc. microRNA (miRNA) expression profile identified genes that were downregulated in ILT3-induced human CD8+ T suppressor cells (Ts) while upregulated in T cells primed in the absence of ILT3. We found that miR-21, miR-30b, and miR-155 target the 3′-untranslated region of genes whose expression was strongly increased in ILT3Fc-induced Ts, such as dual specificity phosphatase 10, B cell CLL/lymphoma 6, and suppressor of cytokine signaling 1, respectively. Transfection of miRNA mimics or inhibitors and site-specific mutagenesis of their 3′-untranslated region binding sites indicated that B cell CLL/lymphoma 6, dual specificity phosphatase 10, and suppressor of cytokine signaling 1 are direct targets of miR-30b, miR-21, and miR-155. Primed CD8+ T cells transfected with miR-21&30b, miR-21&155, or miR-21&30b&155 inhibitors displayed suppressor activity when added to autologous CD3-triggered CD4 T cells. Luciferase reporter assays of miR-21 and miR-155 indicated that their transcription is highly dependent on AP-1. Analysis of activated T cells showed that ILT3Fc inhibited the translocation to the nucleus of the AP-1 subunits, FOSB and c-FOS, and the phosphorylation of ZAP70 and phospholipase C-γ 1. In conclusion, ILT3Fc inhibits T cell activation and induces the generation of Ts targeting multiple inflammatory miRNA pathways.

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Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function

Cited by 241 publications

References 156 publications

Enhanced suppressor of cytokine signaling 3 in arthritic cartilage dysregulates human chondrocyte function

Enhanced suppressor of cytokine signaling 3 in arthritic cartilage dysregulates human chondrocyte function

Identification of Canonical Tyrosine-dependent and Non-canonical Tyrosine-independent STAT3 Activation Sites in the Intracellular Domain of the Interleukin 23 Receptor

Downregulation of Inflammatory MicroRNAs by Ig-like Transcript 3 Is Essential for the Differentiation of Human CD8+ T Suppressor Cells

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