Cutting edge: IFN-producing cells respond to CXCR3 ligands in the presence of CXCL12 and secrete inflammatory chemokines upon activation

Anne Krug, Ravindra Uppaluri, Fabio Facchetti, Brigitte G. Dorner, Kathleen C.F. Sheehan, Robert D. Schreiber, Marina Cella, Marco Colonna

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

Human natural IFN-producing cells (IPC) circulate in the blood and cluster in chronically inflamed lymph nodes around high endothelial venules (HEV). Although L-selectin, CXCR4, and CCR7 are recognized as critical IPC homing mediators, the role of CXCR3 is unclear, since IPC do not respond to CXCR3 ligands in vitro. In this study, we show that migration of murine and human IPC to CXCR3 ligands in vitro requires engagement of CXCR4 by CXCL12. We also demonstrate that CXCL12 is present in human HEV in vivo. Moreover, after interaction with pathogenic stimuli, murine and human IPC secrete high levels of inflammatory chemokines. Thus, IPC migration into inflamed lymph nodes may be initially mediated by L-selectin, CXCL12, and CXCR3 ligands. Upon pathogen encounter, IPC positioning within the lymph node may be further directed by CCR7 and IPC secretion of inflammatory chemokines may attract other IPC, promoting cluster formation in lymph nodes.

Original languageEnglish
Pages (from-to)6079-6083
Number of pages5
JournalJournal of Immunology
Volume169
Issue number11
DOIs
StatePublished - Dec 1 2002

Fingerprint Dive into the research topics of 'Cutting edge: IFN-producing cells respond to CXCR3 ligands in the presence of CXCL12 and secrete inflammatory chemokines upon activation'. Together they form a unique fingerprint.

  • Cite this