Monocyte-like and mature macrophages produce CXCL13 (B cell–attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis

The homeostatic chemokine CXCL13 (also called B cell-attracting chemokine 1 [BCA-1] or B-lymphocyte chemoattractant [BLC]) is constitutively expressed in secondary lymphoid tissue and initiates lymphoid neogenesis when expressed aberrantly in mice. CXCL13 has also been detected in chronic inflammati...

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Bibliographic Details
Published in:Blood 2004-11, Vol.104 (10), p.3021-3027
Main Authors: Carlsen, Hege S., Baekkevold, Espen S., Morton, H. Craig, Haraldsen, Guttorm, Brandtzaeg, Per
Format: Article
Language:English
Subjects:
Adult
Aged
Antigens, CD - metabolism
Antigens, Differentiation, Myelomonocytic - metabolism
Arthritis, Rheumatoid - immunology
Arthritis, Rheumatoid - pathology
Biological and medical sciences
CD11c Antigen - metabolism
Cell Lineage - immunology
Chemokine CXCL13
Chemokines, CXC - metabolism
Child
Female
Fundamental and applied biological sciences. Psychology
General aspects
Humans
Immunopathology
In Vitro Techniques
Inflammation
Inflammatory Bowel Diseases - immunology
Inflammatory Bowel Diseases - pathology
Lymphoid Tissue - immunology
Lymphoid Tissue - pathology
Macrophages - immunology
Macrophages - metabolism
Macrophages - pathology
Male
Medical sciences
Middle Aged
Molecular and cellular biology
Monocytes - immunology
Monocytes - metabolism
Monocytes - pathology
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Summary:The homeostatic chemokine CXCL13 (also called B cell-attracting chemokine 1 [BCA-1] or B-lymphocyte chemoattractant [BLC]) is constitutively expressed in secondary lymphoid tissue and initiates lymphoid neogenesis when expressed aberrantly in mice. CXCL13 has also been detected in chronic inflammation associated with human lymphoid neogenesis, suggesting a pathogenic role. Follicular dendritic cells (FDCs) are generally considered to be the major source of CXCL13 both in normal and aberrant lymphoid tissue. We show here, instead, that most CXCL13-expressing cells in rheumatoid arthritis and ulcerative colitis are of monocyte/macrophage lineage. They are located in irregular lymphoid aggregates within an FDC network, but also within and near smaller collections of B cells in diseased tissue where no FDCs are detected. Some of these CXCL13-expressing cells are CD14+, suggesting derivation from recently extravasated monocytes. Interestingly, monocytes from healthy donors stimulated in vitro with lipopolysaccharide secrete CXCL13. This induced production is enhanced after in vitro maturation of the monocytes toward macrophages but markedly decreased after maturation toward dendritic cells. Together, our findings strongly suggest that newly recruited monocytes/macrophages play a role for lymphoid neogenesis in human inflammatory diseases. Circulating monocytes are therefore potential candidates for future targeted therapy of chronic inflammation.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-02-0701