Increased natural killer cell chemotaxis to CXCL12 in patients with multiple sclerosis

Serrano-Pertierra, Esther; Blanco-Gelaz, Miguel Ángel; Oliva‐Nacarino, Pedro; Martínez–Camblor, Pablo; Villafani, Javier; López‐Larrea, Carlos; Cernuda-Morollón, Eva

doi:10.1016/j.jneuroim.2015.03.007

Cited by 12 publications

(11 citation statements)

References 29 publications

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“…In this regard, while the interference with CXCR4/CXCL12 axis often leads to reduced NK cell protection in pathological conditions, Serrano-Pertierra and colleagues have found increased NK cell chemotaxis in response to CXCL12 in multiple sclerosis patients in the remitting phase and in clinically isolated syndrome patients with respect to relapsing multiple sclerosis patients and healthy controls. This finding has been associated with higher frequencies of NK cells expressing CXCR4 in the blood of the former patients’ cohorts ( 69 ). The enhanced NK cell migration in patients with a less active disease course supports the idea of a neuroprotective role for NK cells in multiple sclerosis ( 70 ).…”

Section: Cxcr4 Receptor/ligand Axismentioning

confidence: 86%

Dysregulation of Chemokine/Chemokine Receptor Axes and NK Cell Tissue Localization during Diseases

et al. 2016

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Chemokines are small chemotactic molecules that play key roles in physiological and pathological conditions. Upon signaling via their specific receptors, chemokines regulate tissue mobilization and trafficking of a wide array of immune cells, including natural killer (NK) cells. Current research is focused on analyzing changes in chemokine/chemokine receptor expression during various diseases to interfere with pathological trafficking of cells or to recruit selected cell types to specific tissues. NK cells are a heterogeneous lymphocyte population comprising several subsets endowed with distinct functional properties and mainly representing distinct stages of a linear development process. Because of their different functional potential, the type of subset that accumulates in a tissue drives the final outcome of NK cell-regulated immune response, leading to either protection or pathology. Correspondingly, chemokine receptors, including CXCR4, CXCR3, and CX3CR1, are differentially expressed by NK cell subsets, and their expression levels can be modulated during NK cell activation. At first, this review will summarize the current knowledge on the contribution of chemokines to the localization and generation of NK cell subsets in homeostasis. How an inappropriate chemotactic response can lead to pathology and how chemokine targeting can therapeutically affect tissue recruitment/localization of distinct NK cell subsets will also be discussed.

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Section: Cxcr4 Receptor/ligand Axismentioning

confidence: 86%

Dysregulation of Chemokine/Chemokine Receptor Axes and NK Cell Tissue Localization during Diseases

et al. 2016

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“…Related to its role in angiogenesis, chemotaxis ( 100 , 101 ), and cell proliferation ( 100 , 102 ), CXCL12/CXCR4 signaling has also been linked to different pathologies including tumor progression and metastasis, as discussed in more detail later.…”

Section: Biological Processes and Signaling Triggered By Cxcl12 Throumentioning

confidence: 99%

Diversity and Inter-Connections in the CXCR4 Chemokine Receptor/Ligand Family: Molecular Perspectives

et al. 2015

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CXCR4 and its ligand CXCL12 mediate the homing of progenitor cells in the bone marrow and their recruitment to sites of injury, as well as affect processes such as cell arrest, survival, and angiogenesis. CXCL12 was long thought to be the sole CXCR4 ligand, but more recently the atypical chemokine macrophage migration inhibitory factor (MIF) was identified as an alternative, non-cognate ligand for CXCR4 and shown to mediate chemotaxis and arrest of CXCR4-expressing T-cells. This has complicated the understanding of CXCR4-mediated signaling and associated biological processes. Compared to CXCL12/CXCR4-induced signaling, only few details are known on MIF/CXCR4-mediated signaling and it remains unclear to which extent MIF and CXCL12 reciprocally influence CXCR4 binding and signaling. Furthermore, the atypical chemokine receptor 3 (ACKR3) (previously CXCR7) has added to the complexity of CXCR4 signaling due to its ability to bind CXCL12 and MIF, and to evoke CXCL12- and MIF-triggered signaling independently of CXCR4. Also, extracellular ubiquitin (eUb) and the viral protein gp120 (HIV) have been reported as CXCR4 ligands, whereas viral chemokine vMIP-II (Herpesvirus) and human β3-defensin (HBD-3) have been identified as CXCR4 antagonists. This review will provide insight into the diversity and inter-connections in the CXCR4 receptor/ligand family. We will discuss signaling pathways initiated by binding of CXCL12 vs. MIF to CXCR4, elaborate on how ACKR3 affects CXCR4 signaling, and summarize biological functions of CXCR4 signaling mediated by CXCL12 or MIF. Also, we will discuss eUb and gp120 as alternative ligands for CXCR4, and describe vMIP-II and HBD-3 as antagonists for CXCR4. Detailed insight into biological effects of CXCR4 signaling und underlying mechanisms, including diversity of CXCR4 ligands and inter-connections with other (chemokine) receptors, is clinically important, as the CXCR4 antagonist AMD3100 has been approved as stem cell mobilizer in specific disease settings.

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“…It will trigger MAPK and PI3K signal pathway [ 10 ] by binding to a G protein-coupled receptor, CXCR4, and contribute to macrophage migration which results from lipid accumulation especially low-density lipoprotein (LDL) [ 11 ]. Additionally, it is identified that different single nucleotide polymorphisms (SNPs) of CXCL12 participates in various disease such as neck and head squamous cell carcinoma [ 12 ], myelodysplastic syndromes [ 13 ], multiple sclerosis [ 14 ], etc. Here, we choose six SNPs (rs1065297, rs1801157, rs266089, rs197452, rs2839693 and rs10793538) of CXCL12 to explore which SNPs are associated with the risk of CAD.…”

Section: Introductionmentioning

confidence: 99%

Variants in the CXCL12 gene was associated with coronary artery disease susceptibility in Chinese Han population

Zhang

Gao

et al. 2017

Oncotarget

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BackgroundCoronary artery disease (CAD) is one of the most serious diseases all around the world. Previous studies have shown the function of CXCL12 in the process of atherosclerosis. The aim of this research is to examine whether variants of CXCL12 contribute to CAD.Materials and MethodsTo examine whether variants of CXCL12 contribute to CAD, we selected 6 single nucleotide polymorphisms (SNPs) of CXCL12, and genotyped by Sequenom MassARRAY technology in 597 CAD patients and 685 healthy control. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age and gender. We also analysis the differences in continuous variables among the subjects with three genotypes of related genes were assessed using the ANOVA.ResultsWe found significant differences in apoB concentrations with rs1065297 and rs10793538 different genotype. In the allele model, rs1065297, rs266089 and rs10793538 in CXCL12 gene associated with the risk of CAD. Stratified according to gender, rs266089 and rs2839693 in CXCL12 gene were associated with the risk of CAD in men, while rs1065297 and rs10793538 in CXCL12 gene were associated with the risk of CAD in women. Stratified according to age, rs197452 decreased the risk of CAD in less than 50 years old group. While in more than 50 years old group, not find significant results. Haplotype analysis shown that haplotype “TGCC” in the block increased CAD risk (OR=1.26, 95%CI: 1.00-1.58, p=0.046).ConclusionThis study provides an evidence for polymorphism of CXCL12 gene associated with CAD development in Chinese Han population.

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Increased natural killer cell chemotaxis to CXCL12 in patients with multiple sclerosis

Cited by 12 publications

References 29 publications

Dysregulation of Chemokine/Chemokine Receptor Axes and NK Cell Tissue Localization during Diseases

Dysregulation of Chemokine/Chemokine Receptor Axes and NK Cell Tissue Localization during Diseases

Diversity and Inter-Connections in the CXCR4 Chemokine Receptor/Ligand Family: Molecular Perspectives

Variants in the CXCL12 gene was associated with coronary artery disease susceptibility in Chinese Han population

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