The Experts below are selected from a list of 23358 Experts worldwide ranked by ideXlab platform
Jason Cosgrove - One of the best experts on this subject based on the ideXlab platform.
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b cell zone reticular cell microenvironments shape CXCL13 gradient formation
Nature Communications, 2020Co-Authors: Mario Novkovic, Jovana Cupovic, Lucas Onder, Natalia Pikor, Jason Cosgrove, Zhaoukun Zhou, Urs Morbe, Stefan Albrecht, Helen MillerAbstract:Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the Chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients. Morphogens such as Chemokines form gradients to direct graded responses and modulate cell behaviors. Here the authors show, using imaging and computer simulation, that the Chemokine CXCL13 originated from follicular reticular cells in the lymph nodes forms both soluble and immobilized gradients to regulate B cell recruitment and migration.
Uwe Koedel - One of the best experts on this subject based on the ideXlab platform.
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the Chemokine CXCL13 is a key regulator of b cell recruitment to the cerebrospinal fluid in acute lyme neuroborreliosis
Journal of Neuroinflammation, 2009Co-Authors: Tobias A Rupprecht, Stefan Kastenbauer, Hanswalter Pfister, Matthias Klein, Andreas Plate, Michaela Adam, Manfed Wick, Caroline Schmidt, Uwe KoedelAbstract:Background: The Chemokine CXCL13 is known to dictate homing and motility of B cells in lymphoid tissue and has been implicated in the formation of ectopic lymphoid tissue in chronic inflammation. Whether it influences B cell trafficking during acute infection, is largely unclear. In previous studies, we showed that (I) CXCL13 levels are markedly increased in the B cell-rich cerebrospinal fluid (CSF) of patients with acute Lyme neuroborreliosis (LNB), and (II) CXCL13 is released by monocytes upon recognition of borrelial outer surface proteins by Tolllike receptor 2. Here, we assessed the role of CXCL13 - in comparison to other Chemokines - in the recruitment of B cells to the CSF of patients with acute LNB. Methods: Measurement of Chemokines was done by ELISA. B cells were isolated from whole blood using magnetic cell separation (MACS). For migration experiments, a modified Boyden chamber assay was used and the migrated B cells were further analysed by FACS. The migration was inhibited either by preincubation of the CSF samples with neutralizing antibodies, heating to 60°C, removal of proteins >3 kDa, or by pre-treatment of the B cells with pertussis toxin. The principal statistical tests used were one-way analysis of variance and Bonferroni test (Chemokine measurements) as well as paired Student's t-test (migration experiments). Results: Measurements of Chemokine levels revealed an increase in three of the four known major B cell chemoattractants CXCL13, CCL19 and CXCL12 in LNB CSF. The CXCL13 CSF:serum ratio, as a measure of the chemotactic gradient, was substantially higher than that of CCL19 and CXCL12. Moreover, the chemotactic activity of LNB CSF was reduced up to 56% after preincubation with a neutralizing CXCL13 antibody, while combined preincubation with antibodies against CXCL13, CCL19, and CXCL12 did not lead to further reduction. Since treatment with pertussis toxin, heating to 60°C, and removal of proteins >3 kDa abrogated the chemotactic activity, further not yet identified Chemokines seem to be involved in B cell recruitment to LNB CSF. Conclusion: Combined, our study suggests a key role of CXCL13 in B cell migration to sites of infection as shown here for the CSF of LNB patients.
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the Chemokine CXCL13 is a key regulator of b cell recruitment to the cerebrospinal fluid in acute lyme neuroborreliosis
Journal of Neuroinflammation, 2009Co-Authors: Tobias A Rupprecht, Stefan Kastenbauer, Hanswalter Pfister, Matthias Klein, Andreas Plate, Michaela Adam, Manfed Wick, Caroline Schmidt, Uwe KoedelAbstract:Background The Chemokine CXCL13 is known to dictate homing and motility of B cells in lymphoid tissue and has been implicated in the formation of ectopic lymphoid tissue in chronic inflammation. Whether it influences B cell trafficking during acute infection, is largely unclear. In previous studies, we showed that (I) CXCL13 levels are markedly increased in the B cell-rich cerebrospinal fluid (CSF) of patients with acute Lyme neuroborreliosis (LNB), and (II) CXCL13 is released by monocytes upon recognition of borrelial outer surface proteins by Toll-like receptor 2. Here, we assessed the role of CXCL13 - in comparison to other Chemokines - in the recruitment of B cells to the CSF of patients with acute LNB.
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borrelia garinii induces CXCL13 production in human monocytes through toll like receptor 2
Infection and Immunity, 2007Co-Authors: Tobias A Rupprecht, Volker Fingerle, Carsten J Kirschning, Bernadette Popp, Stefan Kastenbauer, Hanswalter Pfister, Uwe KoedelAbstract:Recent studies have suggested an important role for the B-cell-attracting Chemokine CXCL13 in the B-cell-dominated cerebrospinal fluid (CSF) infiltrate in patients with neuroborreliosis (NB). High levels of CXCL13 were present in the CSF of NB patients. It has not been clear, however, whether high CSF CXCL13 titers are specific for NB or are a characteristic of other spirochetal diseases as well. Furthermore, the mechanisms leading to the observed CXCL13 expression have not been identified yet. Here we describe similarly elevated CSF CXCL13 levels in patients with neurosyphilis, while pneumococcal meningitis patient CSF do not have high CXCL13 levels. In parallel, challenge of human monocytes in vitro with two of the spirochetal causative organisms, Borrelia garinii (the Borrelia species most frequently found in NB patients) and Treponema pallidum, but not challenge with pneumococci, induced CXCL13 release. This finding implies that a common spirochetal motif is a CXCL13 inducer. Accordingly, we found that the lipid moiety N-palmitoyl-S-(bis[palmitoyloxy]propyl)cystein (Pam3C) (three palmitoyl residues bound to N-terminal cysteine) of the spirochetal lipoproteins is critical for the CXCL13 induction in monocytes. As the Pam3C motif is known to signal via Toll-like receptor 2 (TLR2) and an anti-TLR2 monoclonal antibody blocked CXCL13 production of human monocytes incubated with B. garinii, this suggests that TLR2 is a major mediator of Borrelia-induced secretion of CXCL13 from human monocytes.
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the Chemokine CXCL13 blc a putative diagnostic marker for neuroborreliosis
Neurology, 2005Co-Authors: Tobias A Rupprecht, Stefan Kastenbauer, H W Pfister, Barbara Angele, Bettina Wilske, Uwe KoedelAbstract:Using protein expression profiling, the authors identified an upregulation of the Chemokine B lymphocyte chemoattractant (BLC) in the CSF of patients with neuroborreliosis but not in patients with noninflammatory and various other inflammatory neurologic diseases. This upregulation was confirmed by ELISA, showing increased BLC levels in every neuroborreliosis patient while being undetectable in patients with noninflammatory neurologic diseases. These results point to BLC as a putative additional diagnostic marker for neuroborreliosis.
Helen Miller - One of the best experts on this subject based on the ideXlab platform.
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b cell zone reticular cell microenvironments shape CXCL13 gradient formation
Nature Communications, 2020Co-Authors: Mario Novkovic, Jovana Cupovic, Lucas Onder, Natalia Pikor, Jason Cosgrove, Zhaoukun Zhou, Urs Morbe, Stefan Albrecht, Helen MillerAbstract:Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the Chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients. Morphogens such as Chemokines form gradients to direct graded responses and modulate cell behaviors. Here the authors show, using imaging and computer simulation, that the Chemokine CXCL13 originated from follicular reticular cells in the lymph nodes forms both soluble and immobilized gradients to regulate B cell recruitment and migration.
Guizhen Wang - One of the best experts on this subject based on the ideXlab platform.
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abstract 4066 the Chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution
Cancer Research, 2016Co-Authors: Guizhen Wang, Xin Cheng, Guangbiao ZhouAbstract:More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province the lung cancer incidence is among the highest in China attributed to smoky coal combustion-generated PAH pollution. Here we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a Chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen bezo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in CXCL13 or its receptor, Cxcr5, attenuated BaP-induced lung cancer in mice, demonstrating CXCL139s critical role in PAH-induced lung carcinogenesis. Citation Format: Gui-Zhen Wang, Xin Cheng, Guang-Biao Zhou. The Chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4066.
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the Chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution
eLife, 2015Co-Authors: Guizhen Wang, Xin Cheng, Bo Zhou, Zhesheng Wen, Yunchao Huang, Haobin Chen, Zhiliang Huang, Yongchun Zhou, Lin Feng, Mingming WeiAbstract:More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China, attributed to smoky coal combustion-generated PAH pollution. Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a Chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen benzo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in CXCL13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.
Tobias A Rupprecht - One of the best experts on this subject based on the ideXlab platform.
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the Chemokine CXCL13 in acute neuroborreliosis
Journal of Neurology Neurosurgery and Psychiatry, 2010Co-Authors: Makbule Senel, Tobias A Rupprecht, Hanswalter Pfister, Hayrettin Tumani, Albert C Ludolph, Johannes BrettschneiderAbstract:Objective Recent studies have suggested an important role of the B cell chemoattractant CXCL13 in acute neuroborreliosis (NB). Our aim was to confirm the diagnostic role of CXCL13 and to evaluate its relevance as a therapy response and disease activity marker in NB. Methods CXCL13 was measured in cerebrospinal fluid (CSF) and serum of patients with NB (n=28), systemic borreliosis (SB, n=9), Guillain–Barre syndrome (GBS, n=11), Bell9s palsy (BP, n=19), other cranial nerve palsies (CNP, n=5), cephalgia (C, n=20), bacterial CNS infections (B-CNS-I, n=16) and viral CNS infections (V-CNS-I, n=18). For follow-up studies, serial sample pairs were evaluated from 25 patients with NB (n=56), 11 with B-CNS-I (n=25) and 14 with V-CNS-I (n=36). Results CSF-CXCL13 was significantly elevated in NB compared with other neurological diseases (p Borrelia burgdorferi antibody index showed no significant (p=0.356) change over follow-up. Conclusions The study confirms the relevance of CXCL13 as a diagnostic biomarker of NB and suggests that CSF CXCL13 in NB is linked to duration of disease and could be a marker of disease activity and response to antibiotic therapy.
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the Chemokine CXCL13 is a key regulator of b cell recruitment to the cerebrospinal fluid in acute lyme neuroborreliosis
Journal of Neuroinflammation, 2009Co-Authors: Tobias A Rupprecht, Stefan Kastenbauer, Hanswalter Pfister, Matthias Klein, Andreas Plate, Michaela Adam, Manfed Wick, Caroline Schmidt, Uwe KoedelAbstract:Background: The Chemokine CXCL13 is known to dictate homing and motility of B cells in lymphoid tissue and has been implicated in the formation of ectopic lymphoid tissue in chronic inflammation. Whether it influences B cell trafficking during acute infection, is largely unclear. In previous studies, we showed that (I) CXCL13 levels are markedly increased in the B cell-rich cerebrospinal fluid (CSF) of patients with acute Lyme neuroborreliosis (LNB), and (II) CXCL13 is released by monocytes upon recognition of borrelial outer surface proteins by Tolllike receptor 2. Here, we assessed the role of CXCL13 - in comparison to other Chemokines - in the recruitment of B cells to the CSF of patients with acute LNB. Methods: Measurement of Chemokines was done by ELISA. B cells were isolated from whole blood using magnetic cell separation (MACS). For migration experiments, a modified Boyden chamber assay was used and the migrated B cells were further analysed by FACS. The migration was inhibited either by preincubation of the CSF samples with neutralizing antibodies, heating to 60°C, removal of proteins >3 kDa, or by pre-treatment of the B cells with pertussis toxin. The principal statistical tests used were one-way analysis of variance and Bonferroni test (Chemokine measurements) as well as paired Student's t-test (migration experiments). Results: Measurements of Chemokine levels revealed an increase in three of the four known major B cell chemoattractants CXCL13, CCL19 and CXCL12 in LNB CSF. The CXCL13 CSF:serum ratio, as a measure of the chemotactic gradient, was substantially higher than that of CCL19 and CXCL12. Moreover, the chemotactic activity of LNB CSF was reduced up to 56% after preincubation with a neutralizing CXCL13 antibody, while combined preincubation with antibodies against CXCL13, CCL19, and CXCL12 did not lead to further reduction. Since treatment with pertussis toxin, heating to 60°C, and removal of proteins >3 kDa abrogated the chemotactic activity, further not yet identified Chemokines seem to be involved in B cell recruitment to LNB CSF. Conclusion: Combined, our study suggests a key role of CXCL13 in B cell migration to sites of infection as shown here for the CSF of LNB patients.
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the Chemokine CXCL13 is a key regulator of b cell recruitment to the cerebrospinal fluid in acute lyme neuroborreliosis
Journal of Neuroinflammation, 2009Co-Authors: Tobias A Rupprecht, Stefan Kastenbauer, Hanswalter Pfister, Matthias Klein, Andreas Plate, Michaela Adam, Manfed Wick, Caroline Schmidt, Uwe KoedelAbstract:Background The Chemokine CXCL13 is known to dictate homing and motility of B cells in lymphoid tissue and has been implicated in the formation of ectopic lymphoid tissue in chronic inflammation. Whether it influences B cell trafficking during acute infection, is largely unclear. In previous studies, we showed that (I) CXCL13 levels are markedly increased in the B cell-rich cerebrospinal fluid (CSF) of patients with acute Lyme neuroborreliosis (LNB), and (II) CXCL13 is released by monocytes upon recognition of borrelial outer surface proteins by Toll-like receptor 2. Here, we assessed the role of CXCL13 - in comparison to other Chemokines - in the recruitment of B cells to the CSF of patients with acute LNB.
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borrelia garinii induces CXCL13 production in human monocytes through toll like receptor 2
Infection and Immunity, 2007Co-Authors: Tobias A Rupprecht, Volker Fingerle, Carsten J Kirschning, Bernadette Popp, Stefan Kastenbauer, Hanswalter Pfister, Uwe KoedelAbstract:Recent studies have suggested an important role for the B-cell-attracting Chemokine CXCL13 in the B-cell-dominated cerebrospinal fluid (CSF) infiltrate in patients with neuroborreliosis (NB). High levels of CXCL13 were present in the CSF of NB patients. It has not been clear, however, whether high CSF CXCL13 titers are specific for NB or are a characteristic of other spirochetal diseases as well. Furthermore, the mechanisms leading to the observed CXCL13 expression have not been identified yet. Here we describe similarly elevated CSF CXCL13 levels in patients with neurosyphilis, while pneumococcal meningitis patient CSF do not have high CXCL13 levels. In parallel, challenge of human monocytes in vitro with two of the spirochetal causative organisms, Borrelia garinii (the Borrelia species most frequently found in NB patients) and Treponema pallidum, but not challenge with pneumococci, induced CXCL13 release. This finding implies that a common spirochetal motif is a CXCL13 inducer. Accordingly, we found that the lipid moiety N-palmitoyl-S-(bis[palmitoyloxy]propyl)cystein (Pam3C) (three palmitoyl residues bound to N-terminal cysteine) of the spirochetal lipoproteins is critical for the CXCL13 induction in monocytes. As the Pam3C motif is known to signal via Toll-like receptor 2 (TLR2) and an anti-TLR2 monoclonal antibody blocked CXCL13 production of human monocytes incubated with B. garinii, this suggests that TLR2 is a major mediator of Borrelia-induced secretion of CXCL13 from human monocytes.
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the Chemokine CXCL13 blc a putative diagnostic marker for neuroborreliosis
Neurology, 2005Co-Authors: Tobias A Rupprecht, Stefan Kastenbauer, H W Pfister, Barbara Angele, Bettina Wilske, Uwe KoedelAbstract:Using protein expression profiling, the authors identified an upregulation of the Chemokine B lymphocyte chemoattractant (BLC) in the CSF of patients with neuroborreliosis but not in patients with noninflammatory and various other inflammatory neurologic diseases. This upregulation was confirmed by ELISA, showing increased BLC levels in every neuroborreliosis patient while being undetectable in patients with noninflammatory neurologic diseases. These results point to BLC as a putative additional diagnostic marker for neuroborreliosis.