| First Author | Sharp PE | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 1 | Pages | 340-8 |
| PubMed ID | 23203925 | Mgi Jnum | J:190831 |
| Mgi Id | MGI:5449773 | Doi | 10.4049/jimmunol.1202250 |
| Citation | Sharp PE, et al. (2013) FcgammaRIIb on Myeloid Cells and Intrinsic Renal Cells Rather than B Cells Protects from Nephrotoxic Nephritis. J Immunol 190(1):340-8 |
| abstractText | FcgammaRIIb 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. FcgammaRIIb-deficient mice show exacerbated disease following the induction of nephrotoxic nephritis (NTN). In this study, we determined the cellular origin of the FcgammaRIIb-knockout phenotype by inducing NTN in mice with a deficiency of FcgammaRIIb on either B cells alone (FcgammaRIIB(fl/fl)/CD19Cre(+)) or myeloid cells (FcgammaRIIB(fl/fl)/CEBPalphaCre(+)). Deletion of FcgammaRIIb from B cells did not increase susceptibility to NTN, compared with wild-type (WT) mice, despite higher Ab titers in the FcgammaRIIB(fl/fl)/CD19Cre(+) mice compared with the WT littermate controls. In contrast, mice lacking FcgammaRIIb 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 FcgammaRIIb expression on radioresistant intrinsic renal cells in the protection from NTN was then investigated using bone marrow chimeric mice. FcgammaRIIb(-/-) mice transplanted with FcgammaRIIb(-/-) bone marrow were more susceptible to NTN than WT mice transplanted with FcgammaRIIb(-/-) bone marrow, indicating that the presence of WT intrinsic renal cells protects from NTN. These results demonstrate that FcgammaRIIb on myeloid cells plays a major role in protection from NTN, and therefore, augmentation of FcgammaRIIb on these cells could be a therapeutic target in human Ab-mediated glomerulonephritis. Where there was a lack of FcgammaRIIb on circulating myeloid cells, expression of FcgammaRIIb on intrinsic renal cells provided an additional level of protection from Ab-mediated glomerulonephritis. |
