SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development

Gao, Yu; Liu, Ruining; He, Chenfei; Basile, Juan I.; Vesterlund, Mattias; Wahren‐Herlenius, Marie; Espinoza, Alexander; Hokka-Zakrisson, Cassandra; Zadjali, Fahad; Yoshimura, Akihiko; Karlsson, Mikael C. I.; Carow, Berit; Rottenberg, Martı́n E.

doi:10.3389/fimmu.2021.642173

Cited by 5 publications

(7 citation statements)

References 71 publications

(81 reference statements)

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“…Further, CCL2 may be involved in promoting the progression of cognitive impairment through enhancing excitotoxicity, oxidative stress-induced inflammatory damage, and apoptosis in neuronal cells, affecting glutamate metabolism and inducing microglia activation in the local microenvironment ( 79 – 82 ). SOCS3 is an important negative feedback regulatory protein in the JAK/STAT signaling pathway, a key physiological regulator in natural and acquired immunity, T-lymphocyte differentiation, and immune regulation, and plays a negative feedback regulatory role in immune/inflammatory diseases ( 83 – 85 ). The SOCS3 signaling pathway is also involved in the development of HCC ( 86 , 87 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma

Zhu

Zhu²,

Liu³

et al. 2023

Front. Neurol.

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IntroductionScreening for metabolically relevant differentially expressed genes (DEGs) shared by hepatocellular carcinoma (HCC) and vascular cognitive impairment (VCI) to explore the possible mechanisms of HCC-induced VCI.MethodsBased on metabolomic and gene expression data for HCC and VCI, 14 genes were identified as being associated with changes in HCC metabolites, and 71 genes were associated with changes in VCI metabolites. Multi-omics analysis was used to screen 360 DEGs associated with HCC metabolism and 63 DEGs associated with VCI metabolism.ResultsAccording to the Cancer Genome Atlas (TCGA) database, 882 HCC-associated DEGs were identified and 343 VCI-associated DEGs were identified. Eight genes were found at the intersection of these two gene sets: NNMT, PHGDH, NR1I2, CYP2J2, PON1, APOC2, CCL2, and SOCS3. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. Following principal component analyses (PCA), functional enrichment analyses, immune function analyses, and TMB analyses, these eight DEGs were identified as possibly affecting HCC-induced VCI and the immune microenvironment. As well as gene expression and gene set enrichment analyses (GSEA), a potential drug screen was conducted to investigate the possible mechanisms involved in HCC-induced VCI. The drug screening revealed the potential clinical efficacy of A-443654, A-770041, AP-24534, BI-2536, BMS- 509744, CGP-60474, and CGP-082996.ConclusionHCC-associated metabolic DEGs may influence the development of VCI in HCC patients.

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Section: Discussionmentioning

confidence: 99%

Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma

Zhu

Zhu²,

Liu³

et al. 2023

Front. Neurol.

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“…SOCS3 is also expressed in NKT cells, in response to cytotoxic cytokines such as IL-10 ( 197 ), playing an immunosuppressive role through regulation of cytokine signaling ( 198 ). Finally, SOCS3 expression in thymic stromal cells has also been demonstrated to be important for normal T cell development ( 199 ).…”

Section: Socs Proteins As Regulators Of Immunity and Its Perturbation In Diseasementioning

confidence: 99%

SOCS Proteins in Immunity, Inflammatory Diseases, and Immune-Related Cancer

2021

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Cytokine signaling represents one of the cornerstones of the immune system, mediating the complex responses required to facilitate appropriate immune cell development and function that supports robust immunity. It is crucial that these signals be tightly regulated, with dysregulation underpinning immune defects, including excessive inflammation, as well as contributing to various immune-related malignancies. A specialized family of proteins called suppressors of cytokine signaling (SOCS) participate in negative feedback regulation of cytokine signaling, ensuring it is appropriately restrained. The eight SOCS proteins identified regulate cytokine and other signaling pathways in unique ways. SOCS1–3 and CISH are most closely involved in the regulation of immune-related signaling, influencing processes such polarization of lymphocytes and the activation of myeloid cells by controlling signaling downstream of essential cytokines such as IL-4, IL-6, and IFN-γ. SOCS protein perturbation disrupts these processes resulting in the development of inflammatory and autoimmune conditions as well as malignancies. As a consequence, SOCS proteins are garnering increased interest as a unique avenue to treat these disorders.

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“…However, recent studies suggest that TRIM21 alters T cell development in the thymus ( 63 ). TRIM21 −/− mice had an increased number of thymocytes and a reduced frequency of DN cells ( 18 ). TRIM21 targets suppressor of cytokine signaling-3 (SOCS3) for proteasomal degradation, thus impairing STAT3 activation in TECs ( 64 ).…”

Section: E3 Ubiquitin Ligases In T Cell Developmentmentioning

confidence: 99%

Protein ubiquitination in T cell development

et al. 2022

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As an important form of posttranslational modification, protein ubiquitination regulates a wide variety of biological processes, including different aspects of T cell development and differentiation. During T cell development, thymic seeding progenitor cells (TSPs) in the thymus undergo multistep maturation programs and checkpoints, which are critical to build a functional and tolerant immune system. Currently, a tremendous amount of research has focused on the transcriptional regulation of thymocyte development. However, in the past few years, compelling evidence has revealed that the ubiquitination system also plays a crucial role in the regulation of thymocyte developmental programs. In this review, we summarize recent findings on the molecular mechanisms and cellular pathways that regulate thymocyte ubiquitination and discuss the roles of E3 ligases and deubiquitinating enzymes (DUBs) involved in these processes. Understanding how T cell development is regulated by ubiquitination and deubiquitination will not only enhance our understanding of cell fate determination via gene regulatory networks but also provide potential novel therapeutic strategies for treating autoimmune diseases and cancer.

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SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development

Cited by 5 publications

References 71 publications

Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma

Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma

SOCS Proteins in Immunity, Inflammatory Diseases, and Immune-Related Cancer

Protein ubiquitination in T cell development

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