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 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.
Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, Department of Surgery, Rikshospitalet University Hospital, N-0027 Oslo, Norway. hege.carlsen@klinmed.uio.no.
Hege S
HS
Carlsen
Espen S
ES
Baekkevold
H Craig
HC
Morton
Guttorm
G
Haraldsen
Per
P
Brandtzaeg
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D039521:CD11c Antigen / Q000378:metabolism; D019070:Cell Lineage / Q000276:immunology; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000378:metabolism*; D002648:Child; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039521:CD11c Antigen; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C110663:CXCL13 protein, human