An essential protective role of IL-10 in the immunological mechanism underlying resistance vs susceptibility to lupus induction by dendritic cells and dying cells
Author(s)
Ling, GS
Cook, HT
Botto, M
Lau, YL
Huang, FP
Type
Journal Article
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/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 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/necF/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.
Conclusion. IL-10 protects against the induction of lupus-like renal end-organ damage by down-regulating pathogenic Th1 responses.
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 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/necF/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.
Conclusion. IL-10 protects against the induction of lupus-like renal end-organ damage by down-regulating pathogenic Th1 responses.
Date Issued
2011-07-04
Date Acceptance
2011-07-04
Citation
Rheumatology, 2011, 50 (10), pp.1773-1784
ISSN
1462-0332
Publisher
Oxford University Press
Start Page
1773
End Page
1784
Journal / Book Title
Rheumatology
Volume
50
Issue
10
Copyright Statement
© The Author(s) 2011. Published by Oxford University Press on behalf of The British Society for Rheumatology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Rheumatology
RHEUMATOLOGY
IL-10
Autoimmunity
Lupus
Dendritic cells
Dying cells
MURINE LUPUS
INTERLEUKIN-10 RECEPTOR
AUTOIMMUNE-DISEASE
ERYTHEMATOSUS SLE
PERIPHERAL-BLOOD
INTERFERON-GAMMA
IFN-GAMMA
T-CELLS
MICE
ASSOCIATION
Animals
Antibodies, Antinuclear
Apoptosis
Cells, Cultured
Coculture Techniques
Dendritic Cells
Disease Models, Animal
Disease Susceptibility
Down-Regulation
Immunity, Innate
Interleukin-10
Kidney
Mice
Mice, Inbred C57BL
Mice, Inbred MRL lpr
Mice, Knockout
Necrosis
Proteinuria
Th1 Cells
Arthritis & Rheumatology
1103 Clinical Sciences
1107 Immunology
1117 Public Health And Health Services
Publication Status
Published