The Role of CXCR3 and Its Chemokine Ligands in Skin Disease and Cancer

Kuo, Tsong‐Teh; Zeng, Zhen; Salim, Nazhifah; Mattarollo, Stephen; Wells, James W.; Leggatt, Graham R.

doi:10.3389/fmed.2018.00271

Cited by 126 publications

(107 citation statements)

References 150 publications

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“…Gao et al showed that inhibition of CXCR3 (a CXCL10 receptor) significantly reduced chronic pulmonary inflammation by reducing inflammatory cell recruitment [32]. Studies have also reported that CXCL10 is necessary for cancer cell growth [33,34]. The findings of the present study have shown that CXCL10 and CXCL9 gene upregulation could be a therapeutic target for the maintenance of the normal functioning of cells in the synovium.…”

Section: Discussionsupporting

confidence: 58%

Bioinformatics Analysis and Identification of Genes and Molecular Pathways Involved in Synovial Inflammation in Rheumatoid Arthritis

Xiong

Liu

et al. 2019

Med Sci Monit

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Background Rheumatoid arthritis (RA) has a high prevalence in the elderly population. The genes and pathways in the inflamed synovium in patients with RA are poorly understood. This study aimed to identify differentially expressed genes (DEGs) linked to the progression of synovial inflammation in RA using bioinformatics analysis. Material/Methods Gene expression profiles of datasets GSE55235 and GSE55457 were acquired from the Gene Expression Omnibus (GEO) database. DEGs were identified using Morpheus software, and co-expressed DEGs were identified with Venn diagrams. Protein-protein interaction (PPI) networks were assembled with Cytoscape software and separated into subnetworks using the Molecular Complex Detection (MCODE) algorithm. The functions of the top module were assessed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Results DEGs that were upregulated were significantly enhanced in protein binding, the cell cytosol, organization of the extracellular matrix (ECM), regulation of RNA transcription, and cell adhesion. DEGs that were downregulated were associated with control of the immune response, B-cell and T-cell receptor signaling pathway regulation. KEGG pathway analysis showed that upregulated DEGs enhanced pathways associated with the cell adherens junction, osteoclast differentiation, and hereditary cardiomyopathies. Downregulated DEGs were enriched in primary immunodeficiency, cell adhesion molecules (CAMs), cytokine-cytokine receptor interaction, and hematopoietic cell lineages. Conclusions The findings from this bioinformatics network analysis study identified molecular mechanisms and the key hub genes that may contribute to synovial inflammation in patients with RA.

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Section: Discussionsupporting

confidence: 58%

Bioinformatics Analysis and Identification of Genes and Molecular Pathways Involved in Synovial Inflammation in Rheumatoid Arthritis

Xiong

Liu

et al. 2019

Med Sci Monit

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“…CXCR3 is largely absent from naive T cells but is upregulated upon activation with antigen and recruits activated cells to sites of tissue inflammation in response to its primary ligands: CXCL9, CXCL10, and CXCL11. CXCL9 and CXCL10 are strongly produced in many autoimmune and inflammatory diseases leading to the accumulation of CXCR3+T cells with Th1 phenotypes 33 . CXCR3 has three isoforms in human: CXCR3A, CXCR3B and CXCR3Alt 34 .…”

Section: Discussionmentioning

confidence: 99%

Innate lymphocyte-induced CXCR3B-mediated melanocyte apoptosis is a potential initiator of T-cell autoreactivity in vitiligo

et al. 2019

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T-cells play a crucial role in progression of autoimmunity, including vitiligo, yet the initial steps triggering their activation and tissue damage remain unknown. Here we demonstrate increased presence of type-1 innate lymphoid cells (NK and ILC1)-producing interferon gamma (IFNγ) in the blood and in non-lesional skin of vitiligo patients. Melanocytes of vitiligo patients have strong basal expression of chemokine-receptor-3 (CXCR3) isoform B which is directly regulated by IFNγ. CXCR3B activation by CXCL10 at the surface of cultured human melanocytes induces their apoptosis. The remaining melanocytes, activated by the IFNγ production, express co-stimulatory markers which trigger T-cell proliferation and subsequent anti-melanocytic immunity. Inhibiting the CXCR3B activation prevents this apoptosis and the further activation of T cells. Our results emphasize the key role of CXCR3B in apoptosis of melanocytes and identify CXCR3B as a potential target to prevent and to treat vitiligo by acting at the early stages of melanocyte destruction.

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“…The analysis of inflammatory gene expression in the lungs at the 1-month time point demonstrated that three chemokines, Cxcl9 , Cxcl10 , and Ccl20 , showed the highest differential expression between DMXAA and vehicle-treated mice. CXCL9 and CXCL10 bind the chemokine receptor CXCR3, which is mainly expressed on memory CD4+ and CD8+ and activated CD8+ T cells [ 35 ]. CCL20 binds CCR6, which is mainly expressed on T cells, B cells, and dendritic cells [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Involvement in a Mouse Model of Sjögren’s Syndrome Induced by STING Activation

Papinska

Bagavant

Gmyrek

et al. 2020

IJMS

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Sjögren’s Syndrome (SS), a chronic autoimmune disorder affecting multiple organ systems, is characterized by an elevated type I interferon (IFN) response. Activation of Stimulator of Interferon Genes (STING) protein induces type I IFN and in mice, several features of SS, including anti-nuclear antibodies, sialadenitis, and salivary gland dysfunction. Since lung involvement occurs in one-fifth of SS patients, we investigated whether systemic activation of STING also leads to lung inflammation. Lungs from female C57BL/6 mice injected with the STING agonist 5, 6-Dimethylxanthenone-4-acetic acid (DMXAA), were evaluated for acute and chronic inflammatory responses. Within 4h of DMXAA injection, the expression of Ifnb1, Il6, Tnf, Ifng, and Mx1 was significantly upregulated. At 1 and 2 months post-treatment, lungs showed lymphocytic infiltration in the peri-bronchial regions. The lungs from DMXAA treated mice showed an increased expression of multiple chemokines and an increase in lymphatic endothelial cells. Despite STING expression in bronchial epithelium and cells lining the alveolar wall, bone marrow chimeras between STING knockout and wild type mice showed that STING expression in hematopoietic cells was critical for lung inflammation. Our results suggest that activation of the STING pathway might be involved in SS patients with concomitant salivary gland and lung disease.

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The Role of CXCR3 and Its Chemokine Ligands in Skin Disease and Cancer

Cited by 126 publications

References 150 publications

Bioinformatics Analysis and Identification of Genes and Molecular Pathways Involved in Synovial Inflammation in Rheumatoid Arthritis

Bioinformatics Analysis and Identification of Genes and Molecular Pathways Involved in Synovial Inflammation in Rheumatoid Arthritis

Innate lymphocyte-induced CXCR3B-mediated melanocyte apoptosis is a potential initiator of T-cell autoreactivity in vitiligo

Pulmonary Involvement in a Mouse Model of Sjögren’s Syndrome Induced by STING Activation

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