CXCL6: A potential therapeutic target for inflammation and cancer

Dai, Chun-Lan; Yang, Hong-Xuan; Liu, Qiu-Ping; Rahman, Khalid; Zhang, Hong

doi:10.1007/s10238-023-01152-8

Cited by 7 publications

(2 citation statements)

References 129 publications

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“…Examining chemokine ligand expression in our Olink dataset and in our ROIs, and chemokine receptor expression in our flow cytometry data, confirmed expression of key receptors and also identified potential novel mediators of recruitment in CLE. Based on our Olink and flow cytometry data, we hypothesize that CXCR1 is a key receptor for CXCL6 on proinflammatory CD14+CD16+ APCs, and could be a viable treatment target for CLE, especially given the role of CXCL6 in fibrosis which occurs in DLE and other forms of chronic CLE ( 35 ) as well as in renal interstitial fibrosis ( 36 ). CXCL6 is a particularly interesting target immunologically, given that it may be upregulated by double stranded RNA or IL1β ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease

Shakiba,

Haddadi,

Afshari

et al. 2024

Preprint

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Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics. Flow and Olink data concordantly demonstrated significant increases in T cells and antigen presenting cells (APCs). We also performed spatial transcriptomics and spatial proteomics of punch biopsies using digital spatial profiling (DSP) technology on CLE skin and healthy margin controls to examine discreet locations within the tissue. Spatial and Olink data confirmed elevation of interferon (IFN) and IFN-inducible CXCR3 chemokine ligands. Comparing involved versus uninvolved keratinocytes in CLE samples revealed upregulation of essential inflammatory response genes in areas near interface dermatitis, includingAIM2. Our Olink data confirmed upregulation of Caspase 8, IL-18 which is the final product of AIM2 activation, and induced chemokines including CCL8 and CXCL6 in CLE lesional samples. Chemotaxis assays using PBMCs from healthy and CLE donors revealed that T cells are equally poised to respond to CXCR3 ligands, whereas CD14+CD16+ APC populations are more sensitive to CXCL6 via CXCR1 and CD14+ are more sensitive to CCL8 via CCR2. Taken together, our data map a pathway from keratinocyte injury to lymphocyte recruitment in CLE via AIM2-Casp8-IL-18-CXCL6/CXCR1 and CCL8/CCR2, and IFNG/IFNL1-CXCL9/CXCL11-CXCR3.One Sentence SummaryWe mapped chemokine orchestrators of interface dermatitis in lupus using spatial approaches on archival tissue and confirmed with fresh tissues.

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Section: Discussionmentioning

confidence: 99%

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease

Shakiba,

Haddadi,

Afshari

et al. 2024

Preprint

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“…Granulocyte chemoattractant protein‐2 (GCP‐2) is another name for CXCL6, a pro‐inflammatory cytokine that can increase inflammation by drawing neutrophils. 30 It has been shown that circulating CXCL6 levels were significantly increased in patients with IVDD, and CXCL6 can be used as a biomarker for IVDD. 31 CXCL6 expression was also detected in a study simulating the IVDD environment.…”

Section: Discussionmentioning

confidence: 99%

Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and Mendelian randomization study

Zheng,

Lin,

Wang

et al. 2024

JOR Spine

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BackgroundNumerous investigations have suggested links between circulating inflammatory proteins (CIPs) and spinal degenerative diseases (SDDs), but causality has not been proven. This study used Mendelian randomization (MR) to investigate the causal associations between 91 CIPs and cervical spondylosis (CS), prolapsed disc/slipped disc (PD/SD), spinal canal stenosis (SCS), and spondylolisthesis/spondylolysis.MethodsGenetic variants data for CIPs and SDDs were obtained from the genome‐wide association studies (GWAS) database. We used inverse variance weighted (IVW) as the primary method, analyzing the validity and robustness of the results through pleiotropy and heterogeneity tests and performing reverse MR analysis to test for reverse causality.ResultsThe IVW results with Bonferroni correction indicated that beta‐nerve growth factor (β‐NGF), C‐X‐C motif chemokine 6 (CXCL6), and interleukin‐6 (IL‐6) can increase the risk of CS. Fibroblast growth factor 19 (FGF19), sulfotransferase 1A1 (SULT1A1), and tumor necrosis factor‐beta (TNF‐β) can increase PD/SD risk, whereas urokinase‐type plasminogen activator (u‐PA) can decrease the risk of PD/SD. FGF19 and TNF can increase SCS risk. STAM binding protein (STAMBP) and T‐cell surface glycoprotein CD6 isoform (CD6 isoform) can increase the risk of spondylolisthesis/spondylolysis, whereas monocyte chemoattractant protein 2 (MCP2) and latency‐associated peptide transforming growth factor beta 1 (LAP‐TGF‐β1) can decrease spondylolisthesis/spondylolysis risk.ConclusionsMR analysis indicated the causal associations between multiple genetically predicted CIPs and the risk of four SDDs (CS, PD/SD, SCS, and spondylolisthesis/spondylolysis). This study provides reliable genetic evidence for in‐depth exploration of the involvement of CIPs in the pathogenic mechanism of SDDs and provides novel potential targets for SDDs.

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Causal effects of circulating inflammatory proteins on knee and hip osteoarthritis: A two sample Mendelian randomization study

Lin,

Zheng,

Zhang

et al. 2024

Clin Rheumatol

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CXCL6: A potential therapeutic target for inflammation and cancer

Cited by 7 publications

References 129 publications

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease

Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and Mendelian randomization study

Causal effects of circulating inflammatory proteins on knee and hip osteoarthritis: A two sample Mendelian randomization study

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