The β4GalT1 affects the fibroblast-like synoviocytes invasion in rheumatoid arthritis by modifying N-linked glycosylation of CXCR3

Sun, Chi; Zhu, Xiao Feng; Tao, Tao; Zhang, Dongmei; Wang, Yi; Xu, Hua; Ren, Yunli; Wang, Youhua

doi:10.1016/j.ejcb.2017.02.001

Cited by 8 publications

(9 citation statements)

References 41 publications

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“…It will be important to ascertain whether abnormal blood glucose and insulin levels in individuals with type 1 diabetes contribute to the loss of CXCR3 on memory B cells by studying the effects of ex-vivo culture and by correlating HbA 1c values with chemokine and chemokine receptor expression levels. It is notable in this context that glycosylation of the extracellular domains may increase signalling via CXCR3 [49]. A detailed study of postmortem pancreatic histological samples, available from the nPOD collection, may allow the identification of CXCR3 ++ B cells that trafficked to the pancreas during life, and were thus lost from the periphery.…”

Section: Discussionmentioning

confidence: 99%

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

et al. 2018

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Aims/hypothesisIslet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes.MethodsA total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays.ResultsA disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells.Conclusions/interpretationOur data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration.Electronic supplementary materialThe online version of this article (10.1007/s00125-018-4651-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Section: Discussionmentioning

confidence: 99%

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

et al. 2018

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“…Two additional Tyr residues are present in the NH 2 -terminal extension of CXCR3B at positions 6 and 40. N-glycosylation of CXCR3 expressed on fibroblast-like synoviocytes was confirmed at residues Asn22 and Asn32, with deglycosylation of Asn22 resulting in reduced CXCL10 binding while leaving the CXCR3 expression and stability unaffected ( 91 ).…”

Section: Receptor Interactions Of Ifn-inducible Cxcr3 Ligandsmentioning

confidence: 99%

Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands

et al. 2018

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The inflammatory chemokines CXCL9, CXCL10, and CXCL11 are predominantly induced by interferon (IFN)-γ and share an exclusive chemokine receptor named CXC chemokine receptor 3 (CXCR3). With a prototype function of directing temporal and spatial migration of activated T cells and natural killer cells, and inhibitory effects on angiogenesis, these CXCR3 ligands have been implicated in infection, acute inflammation, autoinflammation and autoimmunity, as well as in cancer. Intense former research efforts led to recent and ongoing clinical trials using CXCR3 and CXCR3 ligand targeting molecules. Scientific evidence has claimed mutual redundancy, ligand dominance, collaboration or even antagonism, depending on the (patho)physiological context. Most research on their in vivo activity, however, illustrates that CXCL9, CXCL10, and CXCL11 each contribute to the activation and trafficking of CXCR3 expressing cells in a non-redundant manner. When looking into detail, one can unravel a multistep machinery behind final CXCR3 ligand functions. Not only can specific cell types secrete individual CXCR3 interacting chemokines in response to certain stimuli, but also the receptor and glycosaminoglycan interactions, major associated intracellular pathways and susceptibility to processing by particular enzymes, among others, seem ligand-specific. Here, we overview major aspects of the molecular properties and regulatory mechanisms of IFN-induced CXCR3 ligands, and propose that their in vivo non-redundancy is a reflection of the unprecedented degree of versatility that seems inherent to the IFN-related CXCR3 chemokine system.

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“…The Arg 216 residue in ECL2 is crucial for activation but does not affect binding or internalization in response to the chemokines ( Colvin et al, 2006 ). N-glycosylation of Asn 22 and Asn 32 residues is required for CXCL10 binding in fibroblast-like synoviocytes expressing CXCR3 ( Sun et al, 2017 ). Figure 3 summarizes the role of various domains of the human CXCR3 receptor.…”

Section: Introductionmentioning

confidence: 99%

Evolution, Expression and Functional Analysis of CXCR3 in Neuronal and Cardiovascular Diseases: A Narrative Review

Satarkar

Patra

2022

Front. Cell Dev. Biol.

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Chemokines form a sophisticated communication network wherein they maneuver the spatiotemporal migration of immune cells across a system. These chemical messengers are recognized by chemokine receptors, which can trigger a cascade of reactions upon binding to its respective ligand. CXC chemokine receptor 3 (CXCR3) is a transmembrane G protein-coupled receptor, which can selectively bind to CXCL9, CXCL10, and CXCL11. CXCR3 is predominantly expressed on immune cells, including activated T lymphocytes and natural killer cells. It thus plays a crucial role in immunological processes like homing of effector cells to infection sites and for pathogen clearance. Additionally, it is expressed on several cell types of the central nervous system and cardiovascular system, due to which it has been implicated in several central nervous system disorders, including Alzheimer’s disease, multiple sclerosis, dengue viral disease, and glioblastoma, as well as cardiovascular diseases like atherosclerosis, Chronic Chagas cardiomyopathy, and hypertension. This review provides a narrative description of the evolution, structure, function, and expression of CXCR3 and its corresponding ligands in mammals and zebrafish and the association of CXCR3 receptors with cardiovascular and neuronal disorders. Unraveling the mechanisms underlying the connection of CXCR3 and disease could help researchers investigate the potential of CXCR3 as a biomarker for early diagnosis and as a therapeutic target for pharmacological intervention, along with developing robust zebrafish disease models.

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The β4GalT1 affects the fibroblast-like synoviocytes invasion in rheumatoid arthritis by modifying N-linked glycosylation of CXCR3

Cited by 8 publications

References 41 publications

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands

Evolution, Expression and Functional Analysis of CXCR3 in Neuronal and Cardiovascular Diseases: A Narrative Review

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