Higher activation of the interferon-gamma signaling pathway in systemic lupus erythematosus patients with a high type I IFN score: relation to disease activity

Liu, Manman; Hao, Shumeng; Wu, Ping; Zhang, Xiaoyan; Xiao, Yichuan; Jiang, Gengru; Huang, Xinfang

doi:10.1007/s10067-018-4138-7

Cited by 38 publications

(35 citation statements)

References 36 publications

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“…Interferon stimulation, particularly IFN- γ , activates overexpression of this gene [ 43 ]. Some studies suggest that GBP1 can be used as a marker for IFN- γ response [ 44 ]. GBP1 gene product can inhibit cellular proliferation and apoptosis in the early cellular inflammatory response [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

IFN-γ Mediates the Development of Systemic Lupus Erythematosus

Liu

Wang

et al. 2020

BioMed Research International

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Objective. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect all organs in the body. It is characterized by overexpression of antibodies against autoantigen. Although previous bioinformatics analyses have identified several genetic factors underlying SLE, they did not discriminate between naive and individuals exposed to anti-SLE drugs. Here, we evaluated specific genes and pathways in active and recently diagnosed SLE population. Methods. GSE46907 matrix downloaded from Gene Expression Omnibus (GEO) was analyzed using R, Metascape, STRING, and Cytoscape to identify differentially expressed genes (DEGs), enrichment pathways, protein-protein interaction (PPI), and hub genes between naive SLE individuals and healthy controls. Results. A total of 134 DEGs were identified, in which 29 were downregulated, whereas 105 were upregulated in active and newly diagnosed SLE cases. GO term analysis revealed that transcriptional induction of the DEGs was particularly enhanced in response to secretion of interferon-γ and interferon-α and regulation of cytokine production innate immune responses among others. KEGG pathway analysis showed that the expression of DEGs was particularly enhanced in interferon signaling, IFN antiviral responses by activated genes, class I major histocompatibility complex (MHC-I) mediated antigen processing and presentation, and amyloid fiber formation. STAT1, IRF7, MX1, OASL, ISG15, IFIT3, IFIH1, IFIT1, OAS2, and GBP1 were the top 10 DEGs. Conclusions. Our findings suggest that interferon-related gene expression and pathways are common features for SLE pathogenesis, and IFN-γ and IFN-γ-inducible GBP1 gene in naive SLE were emphasized. Together, the identified genes and cellular pathways have expanded our understanding on the mechanism underlying development of SLE. They have also opened a new frontier on potential biomarkers for diagnosis, biotherapy, and prognosis for SLE.

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Section: Discussionmentioning

confidence: 99%

IFN-γ Mediates the Development of Systemic Lupus Erythematosus

Liu

Wang

et al. 2020

BioMed Research International

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“…Through a review of documents about lupus and related genes [34–48], 15 core genes related to clinical manifestation were found to be associated in autoimmune disease (Table 1). FCER1G, CLEC7A, MARCO, CLEC7A, PSMB9, and PSMB8 showed apparent correlation with clinical manifestation.…”

Section: Discussionmentioning

confidence: 99%

Immune cell infiltration characteristics and related core genes in lupus nephritis: results from bioinformatic analysis

Cao

Tang

2019

BMC Immunol

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BackgroundLupus nephritis (LN) is a common complication of systemic lupus erythematosus that presents a high risk of end-stage renal disease. In the present study, we used CIBERSORT and gene set enrichment analysis (GSEA) of gene expression profiles to identify immune cell infiltration characteristics and related core genes in LN.ResultsDatasets from the Gene Expression Omnibus, GSE32591 and GSE113342, were downloaded for further analysis. The GSE32591 dataset, which included 32 LN glomerular biopsy tissues and 14 glomerular tissues from living donors, was analyzed by CIBERSORT. Different immune cell types in LN were analyzed by the Limma software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on GSEA were performed by clusterProfiler software. Lists of core genes were derived from Spearman correlation between the most significant GO term and differentially expressed immune cell gene from CIBERSORT. GSE113342 was employed to validate the association between selected core genes and clinical manifestation. Five types of immune cells revealed important associations with LN, and monocytes emerged as having the most prominent differences. GO and KEGG analyses indicated that immune response pathways are significantly enriched in LN. The Spearman correlation indicated that 15 genes, including FCER1G, CLEC7A, MARCO, CLEC7A, PSMB9, and PSMB8, were closely related to clinical features.ConclusionsThis study is the first to identify immune cell infiltration with microarray data of glomeruli in LN by using CIBERSORT analysis and provides novel evidence and clues for further research of the molecular mechanisms of LN.

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“…In a murine model of the disease, chronic circulation of high levels of IFN- γ was demonstrated to trigger a SLE-like syndrome ( 242 ), supporting the role of IFN- γ as a major effector molecule in the pathogenesis of the disease. Recently, the levels of blood IFN- γ has been discovered to correlate positively with anti-ds-DNA levels and SLE activity ( 243 ). As a main source of increased IFN- γ secretion, NK cells are seemed to have an importance in SLE pathogenesis.…”

Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 99%

The Role of Natural Killer Cells in Autoimmune Diseases

et al. 2021

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Natural killer (NK) cells, the large granular lymphocytes differentiated from the common lymphoid progenitors, were discovered in early 1970’s. They are members of innate immunity and were initially defined by their strong cytotoxicity against virus-infected cells and by their important effector functions in anti-tumoral immune responses. Nowadays, NK cells are classified among the recently discovered innate lymphoid cell subsets and have capacity to influence both innate and adaptive immune responses. Therefore, they can be considered as innate immune cells that stands between the innate and adaptive arms of immunity. NK cells don’t express T or B cell receptors and are recognized by absence of CD3. There are two major subgroups of NK cells according to their differential expression of CD16 and CD56. While CD16+CD56dim subset is best-known by their cytotoxic functions, CD16-CD56bright NK cell subset produces a bunch of cytokines comparable to CD4+ T helper cell subsets. Another subset of NK cells with production of interleukin (IL)-10 was named as NK regulatory cells, which has suppressive properties and could take part in immune-regulatory responses. Activation of NK cells is determined by a delicate balance of cell-surface receptors that have either activating or inhibitory properties. On the other hand, a variety of cytokines including IL-2, IL-12, IL-15, and IL-18 influence NK cell activity. NK-derived cytokines and their cytotoxic functions through induction of apoptosis take part in regulation of the immune responses and could contribute to the pathogenesis of many immune mediated diseases including ankylosing spondylitis, Behçet’s disease, multiple sclerosis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus and type-1 diabetes. Dysregulation of NK cells in autoimmune disorders may occur through multiple mechanisms. Thanks to the rapid developments in biotechnology, progressive research in immunology enables better characterization of cells and their delicate roles in the complex network of immunity. As NK cells stand in between innate and adaptive arms of immunity and “bridge” them, their contribution in inflammation and immune regulation deserves intense investigations. Better understanding of NK-cell biology and their contribution in both exacerbation and regulation of inflammatory disorders is a requisite for possible utilization of these multi-faceted cells in novel therapeutic interventions.

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Higher activation of the interferon-gamma signaling pathway in systemic lupus erythematosus patients with a high type I IFN score: relation to disease activity

Cited by 38 publications

References 36 publications

IFN-γ Mediates the Development of Systemic Lupus Erythematosus

IFN-γ Mediates the Development of Systemic Lupus Erythematosus

Immune cell infiltration characteristics and related core genes in lupus nephritis: results from bioinformatic analysis

The Role of Natural Killer Cells in Autoimmune Diseases

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