title: An essential protective role of IL-10 in the immunological mechanism underlying resistance vs. susceptibility to lupus induction by dendritic cells and dying cells.
abstract: OBJECTIVE
  To define the role of IL-10 in lupus pathogenesis, and to understand the immunological mechanisms underlying resistance vs susceptibility to lupus disease induction by dendritic cells (DCs) and dying cells.
  
  
  METHODS
  Groups of IL-10-deficient and normal C57BL/6 mice were injected with syngenic DCs that had ingested necrotic cells prepared by either freeze-thaw cycle (DC/nec(F/T)) or heat shock (DC/nec(H/S)) procedures, or with DC or necrotic cells alone, or with PBS only. Disease development, including proteinuria and renal pathological changes, was monitored. Levels of autoantibodies against different lupus-associated nuclear antigens were measured by ELISAs, and IC deposition in the kidneys was confirmed by immunostaining.
  
  
  RESULTS
  No significant proteinuria was detected in the mice. However, striking renal pathological changes typical of IC-mediated GN were consistently observed in the DC/nec(F/T)-treated IL-10(-/-) mice. These included glomerular hypercellularity and macrophage infiltration, renal IC deposition, circulating kidney-reactive autoantibodies and the presence of immunoglobulin G2 isotype-specific antibody complexes in the diseased kidneys. We demonstrated further that host-derived IL-10 was primarily responsible for protecting against the induction of pathogenic Th1 type of autoantibody responses in the mice.
  
  
  CONCLUSIONS
  IL-10 protects against the induction of lupus-like renal end-organ damage by down-regulating pathogenic Th1 responses.
authors: Department of Medicine, Rheumatology Section, Division of Immunology and Inflammation, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors: Guang-Sheng
authors: GS
authors: Ling
authors: H Terence
authors: HT
authors: Cook
authors: Marina
authors: M
authors: Botto
authors: Yu-Lung
authors: YL
authors: Lau
authors: Fang-Ping
authors: FP
authors: Huang
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D015536:Down-Regulation; D007113:Immunity, Innate / Q000276:immunology*; D016753:Interleukin-10 / Q000172:deficiency / Q000502:physiology*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D009336:Necrosis; D011507:Proteinuria / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; C508609:IL10 protein, human; D016753:Interleukin-10