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CCL21 is a homeostatic lymphoid chemokine instrumental in the recruitment and organization of T cells and dendritic cells into lymphoid T areas. In human secondary lymphoid organs (SLOs), CCL21 is produced by cells distributed throughout the T zone, whereas high endothelial venules (HEVs) lack CCL21 mRNA. A critical question remains whether the development of ectopic lymphoid tissue (ELT) in chronic inflammation recapitulates the features of SLOs. Thus, we systematically investigated in situ the cellular sources of CCL21 in SLOs and ELTs in several human diseases characterized by lymphoid neogenesis. By in situ hybridization and the use of combinatorial cell markers, we show that CCL21-producing vessels in inflamed tissues systematically display typical markers of lymphatic vessels, whereas, as in SLOs, ectopic HEVs do not synthesize detectable levels of CCL21. We also provide first-time evidence that a common pattern of CCL21 expression by CD45-negative myofibroblast-like cells localized in extra-HEV position and organized in a fibroblastic reticular network similarly characterizes human SLOs and organized ELTs. Altogether, our results demonstrate that in humans the pattern of CCL21 production in SLOs is maintained during inflammation and that the phenotypic and functional properties of stromal cells, found in SLO T-cell areas, are reproduced at ectopic sites.

Original publication

DOI

10.2353/ajpath.2007.061275

Type

Journal article

Journal

The American journal of pathology

Publication Date

11/2007

Volume

171

Pages

1549 - 1562

Addresses

Rheumatology Unit, Guy's, King's, and St. Thomas' School of Medicine, London, United Kingdom.

Keywords

Endothelium, Lymphatic, Lymphoid Tissue, Lymph Nodes, Cell Line, Stromal Cells, Lymphatic Vessels, Humans, Arthritis, Rheumatoid, Colitis, Ulcerative, Crohn Disease, Lichen Planus, Psoriasis, Chronic Disease, Adult, Aged, Middle Aged, Female, Male, Chemokine CCL21