{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":45,"searchCount":0},"additional":{"submitter":["Bethunaickan R"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","NIAMS NIH HHS"],"pagination":["4994-5003"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3159403"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["186(8)"],"pubmed_abstract":["Renal infiltration with mononuclear cells is associated with poor prognosis in systemic lupus erythematosus. A renal macrophage/dendritic cell signature is associated with the onset of nephritis in NZB/W mice, and immune-modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. In nephritic NZB/W mice, renal F4/80(hi)/CD11c(int) macrophages are located throughout the interstitium, whereas F4/80(lo)/CD11c(hi) dendritic cells accumulate in perivascular lymphoid aggregates. We show here that F4/80(hi)/CD11c(int) renal macrophages have a Gr1(lo)/Ly6C(lo)/VLA4(lo)/MHCII(hi)/CD43(lo)/CD62L(lo) phenotype different from that described for inflammatory macrophages. At nephritis onset, F4/80(hi)/CD11c(int) cells upregulate cell surface CD11b, acquire cathepsin and matrix metalloproteinase activity, and accumulate large numbers of autophagocytic vacuoles; these changes reverse after the induction of remission. Latex bead labeling of peripheral blood Gr1(lo) monocytes indicates that these are the source of F4/80(hi)/CD11c(int) macrophages. CD11c(hi)/MHCII(lo) dendritic cells are found in the kidneys only after proteinuria onset, turnover rapidly, and disappear rapidly after remission induction. Gene expression profiling of the F4/80(hi)/CD11c(int) population displays increased expression of proinflammatory, regulatory, and tissue repair/degradation-associated genes at nephritis onset that reverses with remission induction. Our findings suggest that mononuclear phagocytes with an aberrant activation profile contribute to tissue damage in lupus nephritis by mediating both local inflammation and excessive tissue remodeling."],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["A unique hybrid renal mononuclear phagocyte activation phenotype in murine systemic lupus erythematosus nephritis."],"pmcid":["PMC3159403"],"funding_grant_id":["R01 AR050401","R01 DK056077","R01 AR049938","R01 DK085241","R01 DK060043","R01 DK085241-01","R01 DK073960","R01 AR049938-05","R01 AI059636-01A2","R01 AI046712"],"pubmed_authors":["Zhang W","Ivashkiv L","Berthier CC","Kretzler M","Bottinger EP","Sahu R","Davidson A","Ramanujam M","Sun Y","Bethunaickan R"],"view_count":["45"],"additional_accession":[]},"is_claimable":false,"name":"A unique hybrid renal mononuclear phagocyte activation phenotype in murine systemic lupus erythematosus nephritis.","description":"Renal infiltration with mononuclear cells is associated with poor prognosis in systemic lupus erythematosus. A renal macrophage/dendritic cell signature is associated with the onset of nephritis in NZB/W mice, and immune-modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. In nephritic NZB/W mice, renal F4/80(hi)/CD11c(int) macrophages are located throughout the interstitium, whereas F4/80(lo)/CD11c(hi) dendritic cells accumulate in perivascular lymphoid aggregates. We show here that F4/80(hi)/CD11c(int) renal macrophages have a Gr1(lo)/Ly6C(lo)/VLA4(lo)/MHCII(hi)/CD43(lo)/CD62L(lo) phenotype different from that described for inflammatory macrophages. At nephritis onset, F4/80(hi)/CD11c(int) cells upregulate cell surface CD11b, acquire cathepsin and matrix metalloproteinase activity, and accumulate large numbers of autophagocytic vacuoles; these changes reverse after the induction of remission. Latex bead labeling of peripheral blood Gr1(lo) monocytes indicates that these are the source of F4/80(hi)/CD11c(int) macrophages. CD11c(hi)/MHCII(lo) dendritic cells are found in the kidneys only after proteinuria onset, turnover rapidly, and disappear rapidly after remission induction. Gene expression profiling of the F4/80(hi)/CD11c(int) population displays increased expression of proinflammatory, regulatory, and tissue repair/degradation-associated genes at nephritis onset that reverses with remission induction. Our findings suggest that mononuclear phagocytes with an aberrant activation profile contribute to tissue damage in lupus nephritis by mediating both local inflammation and excessive tissue remodeling.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Apr","modification":"2024-11-15T16:08:10.36Z","creation":"2019-03-27T00:43:11Z"},"accession":"S-EPMC3159403","cross_references":{"pubmed":["21411733"],"doi":["10.4049/jimmunol.1003010"]}}