NDLI: FcÎ³RIIb on myeloid cells and intrinsic renal cells rather than B cells protects from nephrotoxic nephritis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Martin-Ramirez, Javier Sharp, Phoebe E. H. Tarzi, Ruth M. Pusey, Charles D. Boross, Peter Verbeek, J. Sjef Mangsbo, Sara M. Touw, Ivo P. Cook, H. Terence
Description	Country affiliation: United kingdom Author Affiliation: Sharp PE ( Division of Immunity and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom.)
Abstract	FcÎ³RIIb is the sole inhibitory FcR for IgG in humans and mice, where it is involved in the negative regulation of Ab production and cellular activation. FcÎ³RIIb-deficient mice show exacerbated disease following the induction of nephrotoxic nephritis (NTN). In this study, we determined the cellular origin of the FcÎ³RIIb-knockout phenotype by inducing NTN in mice with a deficiency of FcÎ³RIIb on either B cells alone (FcÎ³RIIB(fl/fl)/CD19Cre(+)) or myeloid cells (FcÎ³RIIB(fl/fl)/CEBP Cre(+)). Deletion of FcÎ³RIIb from B cells did not increase susceptibility to NTN, compared with wild-type (WT) mice, despite higher Ab titers in the FcÎ³RIIB(fl/fl)/CD19Cre(+) mice compared with the WT littermate controls. In contrast, mice lacking FcÎ³RIIb on myeloid cells had exacerbated disease as measured by increased glomerular thrombosis, glomerular crescents, albuminuria, serum urea, and glomerular neutrophil infiltration when compared with WT littermate controls. The role for FcÎ³RIIb expression on radioresistant intrinsic renal cells in the protection from NTN was then investigated using bone marrow chimeric mice. FcÎ³RIIb(-/-) mice transplanted with FcÎ³RIIb(-/-) bone marrow were more susceptible to NTN than WT mice transplanted with FcÎ³RIIb(-/-) bone marrow, indicating that the presence of WT intrinsic renal cells protects from NTN. These results demonstrate that FcÎ³RIIb on myeloid cells plays a major role in protection from NTN, and therefore, augmentation of FcÎ³RIIb on these cells could be a therapeutic target in human Ab-mediated glomerulonephritis. Where there was a lack of FcÎ³RIIb on circulating myeloid cells, expression of FcÎ³RIIb on intrinsic renal cells provided an additional level of protection from Ab-mediated glomerulonephritis.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	1
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	B-lymphocyte Subsets Immunology Glomerulonephritis Prevention & Control Kidney Myeloid Cells Receptors, Igg Physiology Animals Cytology Metabolism Cells, Cultured Genetic Predisposition To Disease Pathology Mice Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Neutrophil Infiltration Genetics Radiation Chimera Deficiency Comparative Study Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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