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Role of CXCL13 in cigarette smoke-induced lymphoid follicle formation and chronic obstructive pulmonary disease

Ken Bracke UGent, Fien Verhamme UGent, Leen Seys UGent, Claudie Bantsimba-Malanda, Danen Mootoosamy Cunoosamy, Ronald Herbst, Hamida Hammad UGent, Bart Lambrecht UGent, Guy Joos UGent and Guy Brusselle UGent (2013) AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 188(3). p.343-355
abstract
Rationale: The B cell-attracting chemokine CXCL13 is an important mediator in the formation of tertiary lymphoid organs (TLOs). Increased numbers of ectopic lymphoid follicles have been observed in lungs of patients with severe chronic obstructive pulmonary disease (COPD). However, the role of these TLOs in the pathogenesis of COPD remains unknown. Objectives: By neutralizing CXCL13 in a mouse model of chronic cigarette smoke (CS) exposure, we aimed at interrogating the link between lymphoid follicles and development of pulmonary inflammation, emphysema, and airway wall remodeling. Methods: We first quantified and localized CXCL13 in lungs of air-or CS-exposed mice and in lungs of never smokers, smokers without airflow obstruction, and patients with COPD by reverse transcriptase-polymerase chain reaction, ELISA, and immunohistochemistry. Next, CXCL13 signaling was blocked by prophylactic or therapeutic administration of anti-CXCL13 antibodies in mice exposed to air or CS for 24 weeks, and several hallmarks of COPD were evaluated. Measurements and Main Results: Both mRNA and protein levels of CXCL13 were increased in lungs of CS-exposed mice and patients with COPD. Importantly, expression of CXCL13 was observed within B-cell areas of lymphoid follicles. Prophylactic and therapeutic administration of anti-CXCL13 antibodies completely prevented the CS-induced formation of pulmonary lymphoid follicles in mice. Interestingly, absence of TLOs attenuated destruction of alveolar walls and inflammation in bronchoalveolar lavage but did not affect airway wall remodeling. Conclusions: CXCL13 is produced within lymphoid follicles of patients with COPD and is crucial for the formation of TLOs. Neutralization of CXCL13 partially protects mice against CS-induced inflammation in bronchoalveolar lavage and alveolar wall destruction.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
lymphoid follicles, CXCL13, DENDRITIC CELLS, B-CELL, INDUCED EMPHYSEMA, MURINE MODEL, PLASMA-CELLS, MICE, COPD, INFLAMMATION, NEOGENESIS, EXPRESSION, chronic obstructive pulmonary disease, cigarette smoke
journal title
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Am. J. Respir. Crit. Care Med.
volume
188
issue
3
pages
343 - 355
Web of Science type
Article
Web of Science id
000322617800016
JCR category
RESPIRATORY SYSTEM
JCR impact factor
11.986 (2013)
JCR rank
1/54 (2013)
JCR quartile
1 (2013)
ISSN
1073-449X
DOI
10.1164/rccm.201211-2055OC
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
additional info
the first two authors contributed equally to this work
copyright statement
I have transferred the copyright for this publication to the publisher
id
4145358
handle
http://hdl.handle.net/1854/LU-4145358
date created
2013-09-26 13:37:09
date last changed
2016-12-19 15:43:40
@article{4145358,
  abstract     = {Rationale: The B cell-attracting chemokine CXCL13 is an important mediator in the formation of tertiary lymphoid organs (TLOs). Increased numbers of ectopic lymphoid follicles have been observed in lungs of patients with severe chronic obstructive pulmonary disease (COPD). However, the role of these TLOs in the pathogenesis of COPD remains unknown.
Objectives: By neutralizing CXCL13 in a mouse model of chronic cigarette smoke (CS) exposure, we aimed at interrogating the link between lymphoid follicles and development of pulmonary inflammation, emphysema, and airway wall remodeling.
Methods: We first quantified and localized CXCL13 in lungs of air-or CS-exposed mice and in lungs of never smokers, smokers without airflow obstruction, and patients with COPD by reverse transcriptase-polymerase chain reaction, ELISA, and immunohistochemistry. Next, CXCL13 signaling was blocked by prophylactic or therapeutic administration of anti-CXCL13 antibodies in mice exposed to air or CS for 24 weeks, and several hallmarks of COPD were evaluated.
Measurements and Main Results: Both mRNA and protein levels of CXCL13 were increased in lungs of CS-exposed mice and patients with COPD. Importantly, expression of CXCL13 was observed within B-cell areas of lymphoid follicles. Prophylactic and therapeutic administration of anti-CXCL13 antibodies completely prevented the CS-induced formation of pulmonary lymphoid follicles in mice. Interestingly, absence of TLOs attenuated destruction of alveolar walls and inflammation in bronchoalveolar lavage but did not affect airway wall remodeling.
Conclusions: CXCL13 is produced within lymphoid follicles of patients with COPD and is crucial for the formation of TLOs. Neutralization of CXCL13 partially protects mice against CS-induced inflammation in bronchoalveolar lavage and alveolar wall destruction.},
  author       = {Bracke, Ken and Verhamme, Fien and Seys, Leen and Bantsimba-Malanda, Claudie and Mootoosamy Cunoosamy, Danen and Herbst, Ronald and Hammad, Hamida and Lambrecht, Bart and Joos, Guy and Brusselle, Guy},
  issn         = {1073-449X},
  journal      = {AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE},
  keyword      = {lymphoid follicles,CXCL13,DENDRITIC CELLS,B-CELL,INDUCED EMPHYSEMA,MURINE MODEL,PLASMA-CELLS,MICE,COPD,INFLAMMATION,NEOGENESIS,EXPRESSION,chronic obstructive pulmonary disease,cigarette smoke},
  language     = {eng},
  number       = {3},
  pages        = {343--355},
  title        = {Role of CXCL13 in cigarette smoke-induced lymphoid follicle formation and chronic obstructive pulmonary disease},
  url          = {http://dx.doi.org/10.1164/rccm.201211-2055OC},
  volume       = {188},
  year         = {2013},
}

Chicago
Bracke, Ken, Fien Verhamme, Leen Seys, Claudie Bantsimba-Malanda, Danen Mootoosamy Cunoosamy, Ronald Herbst, Hamida Hammad, Bart Lambrecht, Guy Joos, and Guy Brusselle. 2013. “Role of CXCL13 in Cigarette Smoke-induced Lymphoid Follicle Formation and Chronic Obstructive Pulmonary Disease.” American Journal of Respiratory and Critical Care Medicine 188 (3): 343–355.
APA
Bracke, Ken, Verhamme, F., Seys, L., Bantsimba-Malanda, C., Mootoosamy Cunoosamy, D., Herbst, R., Hammad, H., et al. (2013). Role of CXCL13 in cigarette smoke-induced lymphoid follicle formation and chronic obstructive pulmonary disease. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 188(3), 343–355.
Vancouver
1.
Bracke K, Verhamme F, Seys L, Bantsimba-Malanda C, Mootoosamy Cunoosamy D, Herbst R, et al. Role of CXCL13 in cigarette smoke-induced lymphoid follicle formation and chronic obstructive pulmonary disease. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2013;188(3):343–55.
MLA
Bracke, Ken, Fien Verhamme, Leen Seys, et al. “Role of CXCL13 in Cigarette Smoke-induced Lymphoid Follicle Formation and Chronic Obstructive Pulmonary Disease.” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 188.3 (2013): 343–355. Print.