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Apoptotic Debris Accumulates on Hematopoietic Cells and Promotes Disease in Murine and Human Systemic Lupus Erythematosus
- Publication Year :
- 2016
- Publisher :
- The University of North Carolina at Chapel Hill University Libraries, 2016.
-
Abstract
- Apoptotic debris, autoantibody, and IgG–immune complexes (ICs) have long been implicated in the inflammation associated with systemic lupus erythematosus (SLE); however, it remains unclear whether they initiate immune-mediated events that promote disease. In this study, we show that PBMCs from SLE patients experiencing active disease, and hematopoietic cells from lupus-prone MRL/lpr and NZM2410 mice accumulate markedly elevated levels of surface-bound nuclear self-antigens. On dendritic cells (DCs) and macrophages (MFs), the self-antigens are part of IgG-ICs that promote FcγRI-mediated signal transduction. Accumulation of IgG-ICs is evident on ex vivo myeloid cells from MRL/lpr mice by 10 wk of age and steadily increases prior to lupus nephritis. IgG and FcγRI play a critical role in disease pathology. Passive transfer of pathogenic IgG into IgG-deficient MRL/lpr mice promotes the accumulation of IgG-ICs prior to significant B cell expansion, BAFF secretion, and lupus nephritis. In contrast, diminishing the burden IgG-ICs in MRL/lpr mice through deficiency in FcγRI markedly improves these lupus pathologies. Taken together, our findings reveal a previously unappreciated role for the cell surface accumulation of IgG-ICs in human and murine lupus.
- Subjects :
- Adult
Male
0301 basic medicine
Mice, Inbred MRL lpr
Immunology
Lupus nephritis
Apoptosis
Inflammation
Autoantigens
Article
Mice
Young Adult
03 medical and health sciences
0302 clinical medicine
immune system diseases
B-Cell Activating Factor
medicine
Animals
Humans
Lupus Erythematosus, Systemic
Immunology and Allergy
B-cell activating factor
skin and connective tissue diseases
B cell
Mice, Knockout
Blood Cells
Lupus erythematosus
Systemic lupus erythematosus
business.industry
Macrophages
Receptors, IgG
Autoantibody
Dendritic Cells
Middle Aged
medicine.disease
Mice, Inbred C57BL
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
Female
medicine.symptom
business
030215 immunology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....50d5188d0e261aeb90fa30ec9ccb4621
- Full Text :
- https://doi.org/10.17615/xwve-c619