An essential protective role of IL-10 in the immunological mechanism underlying resistance vs susceptibility to lupus induction by dendritic cells and dying cells
In: Rheumatology (Oxford, England), Jg. 50 (2011-07-01), Heft 10, S. 1773-1784
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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/necF/T) or heat shock (DC/necH/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 lupusassociated 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/necF/T-treated IL-10-/- mice. These included glomerular hypercellularity and macrophage infiltration, renal IC deposition, circulating kidneyreactive 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. Conclusion: IL-10 protects against the induction of lupus-like renal end-organ damage by downregulating pathogenic Th1 responses. © The Author(s) 2011. Published by Oxford University Press on behalf of The British Society for Rheumatology on behalf of the British Society for Rheumatology.
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An essential protective role of IL-10 in the immunological mechanism underlying resistance vs susceptibility to lupus induction by dendritic cells and dying cells
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Autor/in / Beteiligte Person: | Cook, HT ; Botto, Marina ; Guang Sheng Ling ; Lau, Yu-Lung ; Huang, Fang-Ping |
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Zeitschrift: | Rheumatology (Oxford, England), Jg. 50 (2011-07-01), Heft 10, S. 1773-1784 |
Veröffentlichung: | Oxford University Press, 2011 |
Medientyp: | unknown |
ISSN: | 1462-0332 (print) ; 1462-0324 (print) |
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