FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2511378208> ?p ?o ?g. }

• W2511378208 endingPage "801" @default.
• W2511378208 startingPage "799" @default.
• W2511378208 abstract "Immune complex-mediated diseases, such as systemic lupus erythematosus, commonly affect the kidney and determine disease prognosis. Stamatiades et al. now propose a kidney-specific mechanism for trans-endothelial transport of small immune complexes that activate strategically positioned tissue resident macrophages. Immune complex-mediated diseases, such as systemic lupus erythematosus, commonly affect the kidney and determine disease prognosis. Stamatiades et al. now propose a kidney-specific mechanism for trans-endothelial transport of small immune complexes that activate strategically positioned tissue resident macrophages. IgG antibodies are the key soluble effector molecules of the adaptive immune system. Upon IgG binding to antigen, immune complexes (IC) are formed, allowing the engagement of powerful effector mechanisms, including Fcγ receptor (FcγR) ligation and complement activation. This process ensures effective antimicrobial activity. However, if circulating IC are not adequately cleared by macrophages of the reticuloendothelial system (RES) in the liver and spleen, they may become deposited in tissues and cause inflammation. The kidneys are particularly susceptible to developing inflammation in the presence of circulating IC, as observed in lupus nephritis and in post-streptococcal glomerulonephritis, but the mechanisms underlying this susceptibility have been unclear. In this issue of Cell, Stamatiades et al. demonstrate that in contrast to macrophages in other tissues, kidney macrophages readily take up circulating IC via FcγRs and initiate inflammation (Stamatiades et al., 2016Stamatiades E.G. Tremblay M. Bohm M. Crozet L. Bisht K. Kao D. Coelho C. Fan X. Yewdell W.T. Davidson A. et al.Cell. 2016; (this issue): 991-1003Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar). They further show that this IC uptake is dependent on the unique anatomical position of kidney macrophages that are situated in close apposition to endothelial cells that transport circulating IC to them. IC binding to FcγR results in pro-inflammatory cytokine production and the subsequent recruitment of neutrophils and monocytes, propagating inflammation. Tissue-resident macrophages populate the kidney during embryogenesis. They are derived from CSF1R-dependent yolk-sac precursors and self-renew throughout adult life (Schulz et al., 2012Schulz C. Gomez Perdiguero E. Chorro L. Szabo-Rogers H. Cagnard N. Kierdorf K. Prinz M. Wu B. Jacobsen S.E. Pollard J.W. et al.Science. 2012; 336: 86-90Crossref PubMed Scopus (1737) Google Scholar). A variety of functions have been ascribed to kidney macrophages including clearance of cellular debris, neutrophils, and microbes, and initiation of repair, regeneration, and fibrosis following kidney injury (Rogers et al., 2014Rogers N.M. Ferenbach D.A. Isenberg J.S. Thomson A.W. Hughes J. Nat. Rev. Nephrol. 2014; 10: 625-643Crossref PubMed Scopus (135) Google Scholar). Several lines of evidence suggest that kidney macrophages are involved in IC-induced renal inflammation. For instance, MRL/lpr mice, which spontaneously develop autoantibodies and lupus nephritis, show significant disease amelioration if they are deficient in tissue-resident macrophages due to deletion of CSF1 or its receptor (Lenda et al., 2003Lenda D.M. Kikawada E. Stanley E.R. Kelley V.R. J. Immunol. 2003; 170: 3254-3262Crossref PubMed Scopus (94) Google Scholar). Furthermore, in inducible models of lupus nephritis such as nephrotoxic serum transfer nephritis (NTN), macrophage depletion results in less severe renal pathology (Chalmers et al., 2015Chalmers S.A. Chitu V. Herlitz L.C. Sahu R. Stanley E.R. Putterman C. J. Autoimmun. 2015; 57: 42-52Crossref PubMed Scopus (66) Google Scholar), as does inhibition of FcγR signaling on myeloid cells (Sharp et al., 2013Sharp P.E. Martin-Ramirez J. Mangsbo S.M. Boross P. Pusey C.D. Touw I.P. Cook H.T. Verbeek J.S. Tarzi R.M. J. Immunol. 2013; 190: 340-348Crossref PubMed Scopus (18) Google Scholar). Although these studies have suggested that macrophage cytokine production may play a key role in the pathogenesis of IC-mediated inflammation, the mechanism by which macrophages access IC, the precise identity of the receptors mediating IC binding and the cellular consequences of IC exposure remain unknown. Here, Stamatiades et al., 2016Stamatiades E.G. Tremblay M. Bohm M. Crozet L. Bisht K. Kao D. Coelho C. Fan X. Yewdell W.T. Davidson A. et al.Cell. 2016; (this issue): 991-1003Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar find that, in contrast to dermal macrophages, epidermal Langerhans cells, alveolar macrophages and microglia, renal macrophages rapidly take up circulating IC within minutes of their administration. They confirm that circulating ICs reach the renal interstitium via trans-endothelial transport, where they encounter a population of yolk-sac derived F4/80High, CX3CR1High, CD11bint tissue-resident macrophages positioned along the abluminal side of the peritubular capillary endothelium (Figure 1). Intravital imaging shows that these macrophages extend long, highly motile filopodia along the capillary walls, facilitating surveillance of cargo transported into the interstitium by endothelial cells. The authors also find that IgG IC colocalize with renal macrophages in mice with lupus nephritis (the NZB/W model), suggesting that their findings are relevant to IC-mediated disease in vivo. Kidney macrophages ingest ICs via a FcγRIV-dependent, MyD88- and complement-independent mechanism, and this leads to the secretion of TNF-α, IL1β and CCL2, as well as the upregulation of MHC class II and costimulatory molecules. Circulating nucleic acid-containing IC lead to even greater macrophage activation, pointing to a synergy between FcγR engagement and TLR ligation in this context and providing a mechanistic explanation for the pathogenicity of autoantigen-containing IC in lupus nephritis. This work raises several interesting questions. Macrophages are seeded in tissues during embryogenesis and their precise anatomical position relative to the vasculature differs in different organs (Figure 1). In the kidney, they lie between the endothelium and basement membrane and that position profoundly impacts their function. The mechanisms underlying this specific positioning and the signals that retain macrophages in this compartment and cause them to adopt such a distinctive morphology remain unclear. Given the close relationship between the endothelial cell and macrophage, some of these signals may well be endothelial cell-derived. The authors identify some of the cytokines produced by kidney macrophages in response to IC, but do not determine which of these are responsible for neutrophil and monocyte recruitment. This information would be of use in informing therapeutic strategies in IC-mediated nephritis. This study identifies FcγRIV as the key receptor required for the kidney macrophage response to circulating IC, suggesting that its human ortholog FcγRIIIA may play a similar role. Interestingly, genetic studies in systemic lupus erythematosus show that a single nucleotide polymorphism that encodes a receptor with reduced binding to IgG (FcγRIIIAF158), is associated with increased susceptibility to lupus and to lupus nephritis (Willcocks et al., 2009Willcocks L.C. Smith K.G. Clatworthy M.R. Expert Rev. Mol. Med. 2009; 11: e24Crossref PubMed Scopus (59) Google Scholar). A possible explanation for this seeming discrepancy is that the impact of this low affinity FcγR on IC clearance by RES macrophages is more important than local effects on kidney macrophage activation. Nonetheless, it highlights the need to determine FcγRs expression and function in human kidney macrophages. In summary, the finding of an endothelial cell-macrophage unit responsible for IC handling in the kidney solves the puzzle of why kidneys are susceptible to IC-mediated diseases and highlights this pathway as a potential therapeutic target in these conditions. Immune Monitoring of Trans-endothelial Transport by Kidney-Resident MacrophagesStamatiades et al.CellJuly 28, 2016In BriefKidney-resident macrophages and endothelial cells form an anatomical and functional unit that monitors the transport of proteins and particles according to their size and enables immediate detection of potential threats. Full-Text PDF Open Archive" @default.
• W2511378208 created "2016-09-16" @default.
• W2511378208 creator A5058398382 @default.
• W2511378208 creator A5082524136 @default.
• W2511378208 date "2016-08-01" @default.
• W2511378208 modified "2023-10-05" @default.
• W2511378208 title "Kidney Macrophages: Unique Position Solves a Complex Problem" @default.
• W2511378208 cites W1516554807 @default.
• W2511378208 cites W1978523131 @default.
• W2511378208 cites W2010876644 @default.
• W2511378208 cites W2022776084 @default.
• W2511378208 cites W2048825153 @default.
• W2511378208 cites W2149884235 @default.
• W2511378208 cites W2506440925 @default.
• W2511378208 doi "https://doi.org/10.1016/j.cell.2016.07.047" @default.
• W2511378208 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27518559" @default.
• W2511378208 hasPublicationYear "2016" @default.
• W2511378208 type Work @default.
• W2511378208 sameAs 2511378208 @default.
• W2511378208 citedByCount "5" @default.
• W2511378208 countsByYear W25113782082018 @default.
• W2511378208 countsByYear W25113782082020 @default.
• W2511378208 countsByYear W25113782082022 @default.
• W2511378208 countsByYear W25113782082023 @default.
• W2511378208 crossrefType "journal-article" @default.
• W2511378208 hasAuthorship W2511378208A5058398382 @default.
• W2511378208 hasAuthorship W2511378208A5082524136 @default.
• W2511378208 hasBestOaLocation W25113782081 @default.
• W2511378208 hasConcept C10138342 @default.
• W2511378208 hasConcept C162324750 @default.
• W2511378208 hasConcept C198082294 @default.
• W2511378208 hasConcept C2780091579 @default.
• W2511378208 hasConcept C54355233 @default.
• W2511378208 hasConcept C70721500 @default.
• W2511378208 hasConcept C86803240 @default.
• W2511378208 hasConcept C95444343 @default.
• W2511378208 hasConceptScore W2511378208C10138342 @default.
• W2511378208 hasConceptScore W2511378208C162324750 @default.
• W2511378208 hasConceptScore W2511378208C198082294 @default.
• W2511378208 hasConceptScore W2511378208C2780091579 @default.
• W2511378208 hasConceptScore W2511378208C54355233 @default.
• W2511378208 hasConceptScore W2511378208C70721500 @default.
• W2511378208 hasConceptScore W2511378208C86803240 @default.
• W2511378208 hasConceptScore W2511378208C95444343 @default.
• W2511378208 hasIssue "4" @default.
• W2511378208 hasLocation W25113782081 @default.
• W2511378208 hasLocation W25113782082 @default.
• W2511378208 hasOpenAccess W2511378208 @default.
• W2511378208 hasPrimaryLocation W25113782081 @default.
• W2511378208 hasRelatedWork W1641042124 @default.
• W2511378208 hasRelatedWork W1990804418 @default.
• W2511378208 hasRelatedWork W1993764875 @default.
• W2511378208 hasRelatedWork W2013243191 @default.
• W2511378208 hasRelatedWork W2051339581 @default.
• W2511378208 hasRelatedWork W2082860237 @default.
• W2511378208 hasRelatedWork W2117258802 @default.
• W2511378208 hasRelatedWork W2130076355 @default.
• W2511378208 hasRelatedWork W2151865869 @default.
• W2511378208 hasRelatedWork W4234157524 @default.
• W2511378208 hasVolume "166" @default.
• W2511378208 isParatext "false" @default.
• W2511378208 isRetracted "false" @default.
• W2511378208 magId "2511378208" @default.
• W2511378208 workType "article" @default.