title: CCR7 essentially contributes to the homing of plasmacytoid dendritic cells to lymph nodes under steady-state as well as inflammatory conditions.
abstract: The chemokine receptor CCR7 represents an important determinant for circulating lymphocytes to enter lymph nodes (LN) via high endothelial venules. High endothelial venules also represent the major site of entry for plasmacytoid dendritic cells (pDC). In the steady-state, murine pDC have been suggested to home to LN engaging the chemokine receptors CXCR3, CXCR4, and CCR5, whereas responsiveness to CCR7 ligands is thought to be acquired only upon activation. In this study, we show that already resting pDC express minute amounts of CCR7 that suffice to trigger migration to CCL19/CCL21 in vitro. Upon activation with TLR ligands, CCR7 levels on pDC are strongly increased. Notably, CCR7-deficient mice display substantially reduced pDC counts in LN but not in bone marrow and spleen. Adoptive cell transfer experiments revealed that under both steady-state as well as inflammatory conditions, the homing of CCR7-deficient pDC is severely impaired, indicating that the reduced cell counts of naive pDC observed in CCR7(-/-) mice reflect an intrinsic homing defect of pDC. Together, these observations provide strong evidence that similar to naive lymphocytes, nonstimulated pDC exploit CCR7 to gain entry into LN. This adds to the repertoire of chemokine receptors permitting them to enter diverse tissues.
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. seth.sebastian@mh-hannover.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seth
authors.forename: Linda
authors.initials: L
authors.lastname: Oberdörfer
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hyde
authors.forename: Kirstin
authors.initials: K
authors.lastname: Hoff
authors.forename: Verena
authors.initials: V
authors.lastname: Thies
authors.forename: Tim
authors.initials: T
authors.lastname: Worbs
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmitz
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*
chemical_list: C515371:Ccr7 protein, mouse; D018836:Inflammation Mediators; D054400:Receptors, CCR7; D016201:Receptors, Lymphocyte Homing