title: Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules.
abstract: Recruitment of dendritic cells (DCs) to lymph nodes (LNs) is pivotal to the establishment of immune response. Whereas DCs have been proven to undergo afferent lymphatic pathway to enter LNs from peripheral tissues, a question remains if DCs also migrate into LNs directly from the circulation. Here we demonstrate that plasmacytoid DC (pDC) precursors can transmigrate across high endothelial venules (HEVs) of inflamed LNs in mice. Bacterial infection induces a significant number of pDC and myeloid DC (mDC) precursors into the circulation. Both subsets express a common set of chemokine receptors except CXCR3, display parallel mobilization into the blood, but show distinct trafficking pathway to the LNs. In a short-term homing assay, whereas mDC precursors migrate to peripheral tissues and subsequently to draining LNs, pDC precursors directly enter the LNs in a CXCL9 and E-selectin dependent manner. Tumor necrosis factor-alpha controls not only DC precursor mobilization into the blood but also chemokine up-regulation on LN HEVs. A similar trafficking pathway is observed also in viral infection, and CXCR3(-/-) mice-derived pDC precursors show defective trans-HEV migration. This study clarifies the inflammation-dependent, chemokine-driven distinct property of DC precursor trafficking.
authors.affiliation: Department of Molecular Preventive Medicine & SORST, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsuno
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tetsu
authors.initials: T
authors.lastname: Nishiwaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitabatake
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueha
authors.forename: Shosaku
authors.initials: S
authors.lastname: Narumi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Morikawa
authors.forename: Taichi
authors.initials: T
authors.lastname: Ezaki
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Sho
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D054370:Chemokine CXCL9; D018925:Chemokines / Q000276:immunology; D019743:Chemokines, CXC / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D011425:Propionibacterium acnes / Q000276:immunology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014699:Venules / Q000166:cytology / Q000276:immunology*
chemical_list: C515187:CXCR3 protein, human; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; C485969:Cxcl9 protein, mouse; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha