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Cell. 2016 Aug 11;166(4):991-1003. doi: 10.1016/j.cell.2016.06.058. Epub 2016 Jul 28.

Immune Monitoring of Trans-endothelial Transport by Kidney-Resident Macrophages.

Author information

1
Immunology Program and Ludwig Center, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, NY 10065, USA.
2
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.
3
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.
4
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.
5
Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Strasse 3, 91058 Erlangen, Germany.
6
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.
7
The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
8
Department of Medicine, Recanati Miller Transplant Institute and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
9
Immunotoxicology Team Division, National Institute for Biological Standards and Control, Potters Bar EN6 3QG, UK.
10
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.

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.

PMID:
27477514
PMCID:
PMC4983224
DOI:
10.1016/j.cell.2016.06.058
[Indexed for MEDLINE]
Free PMC Article

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