TY - JOUR
T1 - Immune Monitoring of Trans-endothelial Transport by Kidney-Resident Macrophages
AU - Stamatiades, Efstathios G.
AU - Tremblay, Marie-Eve
AU - Bohm, Mathieu
AU - Crozet, Lucile
AU - Bisht, Kanchan
AU - Kao, Daniela
AU - Coelho, Carolina
AU - Fan, Xiying
AU - Yewdell, William T.
AU - Davidson, Anne
AU - Heeger, Peter S.
AU - Diebold, Sandra
AU - Nimmerjahn, Falk
AU - Geissmann, Frederic
PY - 2016/8/11
Y1 - 2016/8/11
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2016.06.058
DO - 10.1016/j.cell.2016.06.058
M3 - Article
SN - 0092-8674
VL - 166
SP - 991
EP - 1003
JO - Cell
JF - Cell
IS - 4
ER -