title: CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability.
abstract: Lymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability. Here, we have shown that lymphatic collecting vessel permeability is controlled by CCR7 and that the chronic hyperpermeability of collecting vessels observed in Ccr7-/- mice is followed by vessel fibrosis. Reexpression of CCR7 in DCs, however, was sufficient to reverse the development of such fibrosis. IFN regulatory factor 4-positive (IRF4+) DCs constitutively interacted with collecting lymphatics, and selective ablation of this DC subset in Cd11c-Cre Irf4fl/fl mice also rendered lymphatic collecting vessels hyperpermeable and fibrotic. Together, our data reveal that CCR7 plays multifaceted roles in regulating collecting vessel permeability and fibrosis, with one of the key players being IRF4-dependent DCs.
authors.forename: Stoyan
authors.initials: S
authors.lastname: Ivanov
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Scallan
authors.forename: Ki-Wook
authors.initials: KW
authors.lastname: Kim
authors.forename: Kathrin
authors.initials: K
authors.lastname: Werth
authors.forename: Michael W
authors.initials: MW
authors.lastname: Johnson
authors.forename: Brian T
authors.initials: BT
authors.lastname: Saunders
authors.forename: Peter L
authors.initials: PL
authors.lastname: Wang
authors.forename: Emma L
authors.initials: EL
authors.lastname: Kuan
authors.forename: Adam C
authors.initials: AC
authors.lastname: Straub
authors.forename: Melissa
authors.initials: M
authors.lastname: Ouhachi
authors.forename: Erica G
authors.initials: EG
authors.lastname: Weinstein
authors.forename: Jesse W
authors.initials: JW
authors.lastname: Williams
authors.forename: Carlos
authors.initials: C
authors.lastname: Briseño
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Brant E
authors.initials: BE
authors.lastname: Isakson
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Gautier
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davis
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Zinselmeyer
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005355:Fibrosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D042601:Lymphatic Vessels / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D054400:Receptors, CCR7; D000099218:Interferon Regulatory Factor-4; C515371:Ccr7 protein, mouse