Role of CXCL13 in asthma: novel therapeutic target

Chest. 2012 Apr;141(4):886-894. doi: 10.1378/chest.11-0633. Epub 2011 Oct 20.

Abstract

Background: B cells play an important role in allergic asthma. However, the mechanisms by which these cells are activated in the airways remain poorly understood.

Methods: We used a mouse model of ovalbumin (OVA)-induced allergic inflammation to study CXCL13 and to investigate the concentration of this chemokine in the BAL fluid derived from asthmatic and normal control subjects.

Results: We found that OVA-challenged mice upregulate the CXCL13/CXCR5 axis, which is associated with several changes in their airways, including recruitment of B and CD4(+) cells, development of bronchial-associated lymphoid tissue, and airway inflammation. Treating sensitized mice with an anti-CXCL13 antibody reduced cell recruitment, bronchial-associated lymphoid tissue formation, and airways inflammation. Interestingly, measurements of CXCL13 using enzyme-linked immunosorbent assay showed that levels of this cytokine were significantly elevated in BAL fluid from subjects with asthma compared with control subjects (median, 162 [range, 120-296] vs 31 [range, 120-156] pg/mL; P = .005).

Conclusions: All together, these findings suggest that CXCL13 is involved in the allergic airway inflammatory process, and targeting this chemokine may constitute a novel approach in asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies / immunology
  • Asthma / drug therapy*
  • Asthma / physiopathology*
  • B-Lymphocytes / physiology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Chemokine CXCL13 / analysis
  • Chemokine CXCL13 / immunology
  • Chemokine CXCL13 / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Molecular Targeted Therapy
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Young Adult

Substances

  • Antibodies
  • Chemokine CXCL13