Clinical study on CXCL13, CCL17, CCL20 and IL-17 as immune cell migration navigators in relapsing−remitting multiple sclerosis patients

Kalinowska-Łyszczarz, Alicja; Szczuciński, Adam; Pawlak, Mikołaj A.; Losy, Jacek

doi:10.1016/j.jns.2010.09.026

Cited by 29 publications

(19 citation statements)

References 47 publications

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“…11 Production of the chemoattractants CXCL10, CXCL13, and CCL20 in the CNS has been associated with B-cell recruitment, distribution, and reactivity in MS. [24][25][26] We compared the presence of B cells that express the chemokine receptors that correspond to these ligands, CXCR3 + (CXCL10), CXCR5 + (CXCL13), and CCR6 + (CCL20), between paired blood, CSF, and meningeal and brain tissues from 10 MS patients (see Table 1). 11 Production of the chemoattractants CXCL10, CXCL13, and CCL20 in the CNS has been associated with B-cell recruitment, distribution, and reactivity in MS. [24][25][26] We compared the presence of B cells that express the chemokine receptors that correspond to these ligands, CXCR3 + (CXCL10), CXCR5 + (CXCL13), and CCR6 + (CCL20), between paired blood, CSF, and meningeal and brain tissues from 10 MS patients (see Table 1).…”

Section: Cxcr3-expressing B Cells Are Selectively Enriched In Distincmentioning

confidence: 99%

“…Enhanced chemotaxis is one of the key mechanisms by which B cells can enter distinct CNS compartments of MS patients. 11 Production of the chemoattractants CXCL10, CXCL13, and CCL20 in the CNS has been associated with B-cell recruitment, distribution, and reactivity in MS. [24][25][26] We compared the presence of B cells that express the chemokine receptors that correspond to these ligands, CXCR3 + (CXCL10), CXCR5 + (CXCL13), and CCR6 + (CCL20), between paired blood, CSF, and meningeal and brain tissues from 10 MS patients (see Table 1). To realize this, single-cell suspensions were obtained from autopsied brain compartments using a standardized protocol.…”

Section: Cxcr3-expressing B Cells Are Selectively Enriched In Distincmentioning

confidence: 99%

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Induction of brain‐infiltrating T‐bet–expressing B cells in multiple sclerosis

Langelaar

Rijvers

Janssen

et al. 2019

Annals of Neurology

136

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Objective Results from anti‐CD20 therapies demonstrate that B‐ and T‐cell interaction is a major driver of multiple sclerosis (MS). The local presence of B‐cell follicle‐like structures and oligoclonal bands in MS patients indicates that certain B cells infiltrate the central nervous system (CNS) to mediate pathology. Which peripheral triggers underlie the development of CNS‐infiltrating B cells is not fully understood. Methods Ex vivo flow cytometry was used to assess chemokine receptor profiles of B cells in blood, cerebrospinal fluid, meningeal, and brain tissues of MS patients (n = 10). Similar analyses were performed for distinct memory subsets in the blood of untreated and natalizumab‐treated MS patients (n = 38). To assess T‐bet(CXCR3)+ B‐cell differentiation, we cultured B cells from MS patients (n = 21) and healthy individuals (n = 34) under T helper 1‐ and TLR9‐inducing conditions. Their CNS transmigration capacity was confirmed using brain endothelial monolayers. Results CXC chemokine receptor 3 (CXCR3)‐expressing B cells were enriched in different CNS compartments of MS patients. Treatment with the clinically effective drug natalizumab prevented the recruitment of CXCR3high IgG1+ subsets, corresponding to their increased ability to cross CNS barriers in vitro. Blocking of interferon‐γ (IFNγ) reduced the transmigration potential and antigen‐presenting function of these cells. IFNγ‐induced B cells from MS patients showed increased T‐bet expression and plasmablast development. Additional TLR9 triggering further upregulated T‐bet and CXCR3, and was essential for IgG1 switching. Interpretation This study demonstrates that T‐bethigh IgG1+ B cells are triggered by IFNγ and TLR9 signals, likely contributing to enhanced CXCR3‐mediated recruitment and local reactivity in the CNS of MS patients. ANN NEUROL 2019;86:264–278

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Section: Cxcr3-expressing B Cells Are Selectively Enriched In Distincmentioning

confidence: 99%

Section: Cxcr3-expressing B Cells Are Selectively Enriched In Distincmentioning

confidence: 99%

Induction of brain‐infiltrating T‐bet–expressing B cells in multiple sclerosis

Langelaar

Rijvers

Janssen

et al. 2019

Annals of Neurology

136

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“…MS is characterized by symptoms like mood disorder, fatigue, vision changes, muscle weakness, and motor changes [15]. Chemokines like IL-17, chemokine (C-C motif) ligand 17 (CCL17), and CCL20 are suggested as major mediators in MS neuroinflammation and pathology [16]. …”

Section: Introductionmentioning

confidence: 99%

Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

Bhullar

Rupasinghe

2013

Oxidative Medicine and Cellular Longevity

347

194

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Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders.

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“…The pathogenesis of MS involves disturbed cytokine production, including upregulation of proinflammatory cytokines [IL-6, IL-17, IL-1, tumor necrosis factor (TNF)-α, IL-22 and CCL20], and downregulation of anti-inflammatory cytokines (IL-3, IL-4 and IL-10) [2,3,4,5,6]. Proinflammatory cytokines accumulate in MS lesions, suggesting that their increased production may impair cellular defense mechanisms, facilitating demyelination [2,7,8].…”

Section: Introductionmentioning

confidence: 99%

Decreased Level of sRAGE in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset

Glasnović¹,

Cvija

Stojić³

et al. 2014

Neuroimmunomodulation

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Objectives: Receptor for advanced glycation end products (RAGE) ligands/RAGE interactions have been proposed to have a pathogenic role in neuroinflammatory disorders. Our study aimed to assess changes in high-mobility group box (HMGB)1 and its receptor RAGE in peripheral blood (PBL) and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) at the disease onset compared with control subjects. Methods: PBL and CSF were collected from control subjects (n = 30) and MS patients (n = 27) at clinical onset. Soluble RAGE (sRAGE), HMGB1, S100 calcium-binding protein A12 (S100A12), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured in the CSF and plasma by enzyme-linked immunosorbent assay. Gene expression in PBL mononuclear cells (PBMCs) was detected by quantitative PCR for RAGE, HMGB1, S100A12 and several proinflammatory/immunoregulatory cytokines. Results: We found a significantly lower expression of IL-10 (p = 0.031) in the PBMCs of MS patients. The level of sRAGE in the CSF of MS patients was lower (p = 0.021), with the ability to discriminate between MS patients and control subjects. Moreover, PBMC gene expression for HMGB1 and S100A12 positively correlated with IL-6. Conclusions: Our study confirmed that the cytokine network is disturbed in PBL and CSF at MS clinical onset. The deregulated HMGB1/RAGE axis found in our study may present an early pathogenic event in MS, proposing sRAGE as a possible novel therapeutic strategy for MS treatment.

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Clinical study on CXCL13, CCL17, CCL20 and IL-17 as immune cell migration navigators in relapsing−remitting multiple sclerosis patients

Cited by 29 publications

References 47 publications

Induction of brain‐infiltrating T‐bet–expressing B cells in multiple sclerosis

Induction of brain‐infiltrating T‐bet–expressing B cells in multiple sclerosis

Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

Decreased Level of sRAGE in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset

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