title: Immune Monitoring of Trans-endothelial Transport by Kidney-Resident Macrophages.
abstract: Small immune complexes cause type III hypersensitivity reactions that frequently result in tissue injury. The responsible mechanisms, however, remain unclear and differ depending on target organs. Here, we identify a kidney-specific anatomical and functional unit, formed by resident macrophages and peritubular capillary endothelial cells, which monitors the transport of proteins and particles ranging from 20 to 700 kDa or 10 to 200 nm into the kidney interstitium. Kidney-resident macrophages detect and scavenge circulating immune complexes "pumped" into the interstitium via trans-endothelial transport and trigger a FcγRIV-dependent inflammatory response and the recruitment of monocytes and neutrophils. In addition, FcγRIV and TLR pathways synergistically "super-activate" kidney macrophages when immune complexes contain a nucleic acid. These data identify a physiological function of tissue-resident kidney macrophages and a basic mechanism by which they initiate the inflammatory response to small immune complexes in the kidney.
authors.affiliation: Immunology Program and Ludwig Center, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA.
authors.forename: Efstathios G
authors.initials: EG
authors.lastname: Stamatiades
authors.affiliation: Département de Médecine Moléculaire, Université Laval, Laval, QC G1V 0A6, Canada; Axe Neurosciences, Centre de Recherche du CHU de Québec, Québec, QC G1V 4G2, Canada.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Tremblay
authors.affiliation: Immunology Program and Ludwig Center, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA; Division of Immunology, Infection and Center for Molecular and Cellular Biology of Inflammation, Inflammatory Diseases King's College London, London SE1 1UL, UK.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bohm
authors.affiliation: Immunology Program and Ludwig Center, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Lucile
authors.initials: L
authors.lastname: Crozet
authors.affiliation: Département de Médecine Moléculaire, Université Laval, Laval, QC G1V 0A6, Canada; Axe Neurosciences, Centre de Recherche du CHU de Québec, Québec, QC G1V 4G2, Canada.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Bisht
authors.affiliation: Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Strasse 3, 91058 Erlangen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kao
authors.affiliation: Immunology Program and Ludwig Center, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Coelho
authors.affiliation: Immunology Program and Ludwig Center, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA; Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA.
authors.forename: Xiying
authors.initials: X
authors.lastname: Fan
authors.affiliation: Immunology Program and Ludwig Center, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Yewdell
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Davidson
authors.affiliation: Department of Medicine, Recanati Miller Transplant Institute and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Heeger
authors.affiliation: Immunotoxicology Team Division, National Institute for Biological Standards and Control, Potters Bar EN6 3QG, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Diebold
authors.affiliation: Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Strasse 3, 91058 Erlangen, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.affiliation: Immunology Program and Ludwig Center, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA; Division of Immunology, Infection and Center for Molecular and Cellular Biology of Inflammation, Inflammatory Diseases King's College London, London SE1 1UL, UK; Weill Cornell Graduate School of Medical Sciences, 1300 York Avenue, New York, NY 10065, USA. Electronic address: geissmaf@mskcc.org.
authors.forename: Frederic
authors.initials: F
authors.lastname: Geissmann
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex; D042783:Endothelial Cells; D007105:Immune Complex Diseases / Q000276:immunology*; D007668:Kidney / Q000166:cytology* / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; C522404:Fcgr4 protein, mouse; D017452:Receptors, IgG