FcγRIIb on Myeloid Cells and Intrinsic Renal Cells Rather than B Cells Protects from Nephrotoxic Nephritis
2013 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 190, no 1, 340-348 p.Article in journal (Refereed) Published
FcγRIIb 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. FcγRIIb-deficient mice show exacerbated disease following the induction of nephrotoxic nephritis (NTN). In this study, we determined the cellular origin of the FcγRIIb-knockout phenotype by inducing NTN in mice with a deficiency of FcγRIIb on either B cells alone (FcγRIIBfl/fl/CD19Cre+) or myeloid cells (FcγRIIBfl/fl/CEBPαCre+). Deletion of FcγRIIb from B cells did not increase susceptibility to NTN, compared with wild-type (WT) mice, despite higher Ab titers in the FcγRIIBfl/fl/CD19Cre+ mice compared with the WT littermate controls. In contrast, mice lacking FcγRIIb 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 FcγRIIb expression on radioresistant intrinsic renal cells in the protection from NTN was then investigated using bone marrow chimeric mice. FcγRIIb−/− mice transplanted with FcγRIIb−/− bone marrow were more susceptible to NTN than WT mice transplanted with FcγRIIb−/− bone marrow, indicating that the presence of WT intrinsic renal cells protects from NTN. These results demonstrate that FcγRIIb on myeloid cells plays a major role in protection from NTN, and therefore, augmentation of FcγRIIb on these cells could be a therapeutic target in human Ab-mediated glomerulonephritis. Where there was a lack of FcγRIIb on circulating myeloid cells, expression of FcγRIIb on intrinsic renal cells provided an additional level of protection from Ab-mediated glomerulonephritis.
Place, publisher, year, edition, pages
2013. Vol. 190, no 1, 340-348 p.
Rheumatology and Autoimmunity Immunology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-187545DOI: 10.4049/jimmunol.1202250PubMedID: 23203925OAI: oai:DiVA.org:uu-187545DiVA: diva2:575093