Differential Modulation of Stimulatory and Inhibitory Fcγ Receptors on Human Monocytes by Th1 and Th2 Cytokines

Pricop, Luminita; Redecha, Patricia; Teillaud, Jean‐Luc; Frey, Jürgen; Fridman, Wolf Herman; Sautès-Fridman, Catheriné; Salmon, Jane E.

doi:10.4049/jimmunol.166.1.531

Cited by 214 publications

(192 citation statements)

References 36 publications

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“…The 158 kb assembled contig that contains Fc␥RIIB, FcRL, DUSP12 and ATF6 genes is available in the NCBI database (AL 359541). binding sites which could explain the IL4 responsiveness of Fc␥RIIB expression 29 but not the differential expression of the two genes.…”

Section: Resultsmentioning

confidence: 95%

Genomic organization of classical human low-affinity Fcγ receptor genes

Edberg

et al. 2002

Genes Immun

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Section: Resultsmentioning

confidence: 95%

Genomic organization of classical human low-affinity Fcγ receptor genes

Edberg

et al. 2002

Genes Immun

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“…Indeed, IVIG was not effective in protecting FcgRIIb 2/2 mice from NTN, indicating that this is an important mechanism of action for IVIG (20). Th2 cytokines, such as IL-4, are known to increase myeloid expression of FcgRIIb (21). Recently, it has been determined that the sialylated IgG component of human IVIG binds to a lectin receptor dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin on dendritic cells, leading to the secretion of IL-33, which upregulates IL-4 secretion by basophils and leads to the increased expression of FcgRIIb on myeloid cells (22).…”

Section: Discussionmentioning

confidence: 99%

FcγRIIb on Myeloid Cells and Intrinsic Renal Cells Rather than B Cells Protects from Nephrotoxic Nephritis

Sharp

Martín-Ramírez

Mangsbo

et al. 2013

The Journal of Immunology

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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.

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“…For example, upon coligation of Fc␥RIIb with the BCR by IgG immune complexes, Fc␥RIIb recruits and activates the SHIP and negatively regulates B cell activation and proliferation, thereby providing a critical mechanism for the feedback inhibition of IgG production (4). On monocytes and macrophages, Fc␥RIIb down-regulates Fc␥RIIa (CD32A)-and Fc␥RIIIa (CD16A)-mediated phagocytosis when coligated with those activating receptors (2,5,6). Fc␥RIIb also down-modulates mast cell activation by the high-affinity IgE FcR (7,8).…”

Section: T He Only Inhibitory Igg Fcr In the Classical Fcr Family (1mentioning

confidence: 99%

Expression Profile of FcγRIIb on Leukocytes and Its Dysregulation in Systemic Lupus Erythematosus

Yang

et al. 2007

The Journal of Immunology

166

150

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FcγRIIb (CD32B, Online Mendelian Inheritance in Man 604590), an IgG FcR with a tyrosine-based inhibitory motif, plays a critical role in the balance of tolerance and autoimmunity in murine models. However, the high degree of homology between FcγRIIb and FcγRIIa in humans and the lack of specific Abs to differentiate them have hampered study of the normal expression profile of FcγRIIb and its potential dysregulation in autoimmune diseases such as systemic lupus erythematosus (SLE). Using our newly developed anti-FcγRIIb mAb 4F5 which does not react with FcγRIIa, we found that FcγRIIb is expressed on the cell surface of circulating B lymphocytes, monocytes, neutrophils, myeloid dendritic cells (DCs), and at very low levels on plasmacytoid DCs from some donors. Normal donors with the less frequent 2B.4 promoter haplotype have higher FcγRIIb expression on monocytes, neutrophils, and myeloid DCs similar to that reported for B lymphocytes, indicating that FcγRIIb expression on both myeloid and lymphoid cells is regulated by the naturally occurring regulatory single nucleotide polymorphisms in the FCGR2B promoter. FcγRIIb expression in normal controls is up-regulated on memory B lymphocytes compared with naive B lymphocytes. In contrast, in active SLE, FcγRIIb is significantly down-regulated on both memory and plasma B lymphocytes compared with naive and memory/plasma B lymphocytes from normals. Similar down-regulation of FcγRIIb on myeloid-lineage cells in SLE was not seen. Our studies demonstrate the constitutive regulation of FcγRIIb by natural gene polymorphisms and the acquired dysregulation in SLE autoimmunity, which may identify opportunities for using this receptor as a therapeutic target.

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Differential Modulation of Stimulatory and Inhibitory Fcγ Receptors on Human Monocytes by Th1 and Th2 Cytokines

Cited by 214 publications

References 36 publications

Genomic organization of classical human low-affinity Fcγ receptor genes

Genomic organization of classical human low-affinity Fcγ receptor genes

FcγRIIb on Myeloid Cells and Intrinsic Renal Cells Rather than B Cells Protects from Nephrotoxic Nephritis

Expression Profile of FcγRIIb on Leukocytes and Its Dysregulation in Systemic Lupus Erythematosus

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