CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflammatory lesions with lymphoid neogenesis

Antonio Manzo, Serena Bugatti, Roberto Caporali, Remko Prevo, David G. Jackson, Mariagrazia Uguccioni, Christopher D. Buckley, Carlomaurizio Montecucco, Costantino Pitzalis

Research output: Contribution to journalArticle

Abstract

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 (SDOs), 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 SDDs. 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 languageEnglish
Pages (from-to)1549-1562
Number of pages14
JournalAmerican Journal of Pathology
Volume171
Issue number5
DOIs
Publication statusPublished - Nov 2007

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Venules
Inflammation
T-Lymphocytes
Lymphatic Vessels
Myofibroblasts
Stromal Cells
Chemokines
Dendritic Cells
In Situ Hybridization
Messenger RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflammatory lesions with lymphoid neogenesis. / Manzo, Antonio; Bugatti, Serena; Caporali, Roberto; Prevo, Remko; Jackson, David G.; Uguccioni, Mariagrazia; Buckley, Christopher D.; Montecucco, Carlomaurizio; Pitzalis, Costantino.

In: American Journal of Pathology, Vol. 171, No. 5, 11.2007, p. 1549-1562.

Research output: Contribution to journalArticle

Manzo, Antonio ; Bugatti, Serena ; Caporali, Roberto ; Prevo, Remko ; Jackson, David G. ; Uguccioni, Mariagrazia ; Buckley, Christopher D. ; Montecucco, Carlomaurizio ; Pitzalis, Costantino. / CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflammatory lesions with lymphoid neogenesis. In: American Journal of Pathology. 2007 ; Vol. 171, No. 5. pp. 1549-1562.
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AU - Bugatti, Serena

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