FcγRI (CD64) Contributes Substantially to Severity of Arthritis, Hypersensitivity Responses, and Protection from Bacterial Infection

Ioan-Facsinay, A.; Kimpe, Sjef J. De; Hellwig, Sandra M.M.; Lent, P.L. van; Hofhuis, F. M. A.; Ojik, Heidi H. van; Sedlik, Christine; Silveira, Samareh Azeredo da; Gerber, Jeffrey S.; Jong, Yuh-Jyh; Roozendaal, Ramon; Aarden, Lucien A.; Berg, Wim B. van den; Saito, Takashi; Mosser, David M.; Amigorena, Sébastian; Izui, Shozo; Ommen, G-J B van; Vugt, Michèle van; Winkel, Jan G. J. van de; Verbeek, J. Sjef

doi:10.1016/s1074-7613(02)00294-7

Cited by 280 publications

(279 citation statements)

References 34 publications

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“…The specific role for Fc␥RI in chondrocyte death was confirmed in the present study, since IFN␥ overexpression in Fc␥RIII Ϫ/Ϫ mice resulted in high levels of chondrocyte death similar to those in controls. Since Fc␥RI is exclusively expressed on macrophages (37), this proves that macrophage activation is crucial in the induction of chondrocyte death.…”

Section: Discussionmentioning

confidence: 80%

Joint inflammation and chondrocyte death become independent of Fcγ receptor type III by local overexpression of interferon‐γ during immune complex–mediated arthritis

Nabbe¹,

Boross²,

Holthuysen³

et al. 2005

Arthritis & Rheumatism

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Objective. It has previously been shown that the onset and the degree of joint inflammation during immune complex (IC)-mediated arthritis depend on Fc␥ receptor type III (Fc␥RIII). Local adenoviral overexpression of interferon-␥ (IFN␥) in the knee joint prior to onset of IC-mediated arthritis aggravated severe cartilage destruction. In Fc␥RI Ϫ/Ϫ mice, however, chondrocyte death was not enhanced by IFN␥, whereas matrix metalloproteinase (MMP)-mediated aggrecan breakdown was markedly elevated, suggesting a role for the activating Fc␥RIII in the latter process. We undertook this study to determine the role of Fc␥RIII in joint inflammation and severe cartilage destruction in IFN␥-stimulated IC-mediated arthritis, using Fc␥RIII ؊/؊ mice.Methods. Fc␥RIII ؊/؊ and wild-type (WT) mice were injected in the knee joint with recombinant adenovirus encoding murine IFN␥ (AdIFN␥) or with adenovirus encoding enhanced green fluorescent protein 1 day prior to induction of IC-mediated arthritis. Histologic sections were obtained 3 days after arthritis onset to study inflammation and cartilage damage. MMPmediated expression of the VDIPEN neoepitope was detected by immunolocalization. Chemokine and Fc␥R expression levels were determined in synovial washouts and synovium, respectively.Results. Injection of AdIFN␥ in naive knee joints markedly increased levels of messenger RNA for Fc␥RI, Fc␥RII, and Fc␥RIII. Upon IFN␥ overexpression prior to induction of IC-mediated arthritis, joint inflammation was similar in Fc␥RIII ؊/؊ and WT mice. The percentage of macrophages in the knee joint was increased, which correlated with high concentrations of the macrophage attractant macrophage inflammatory protein 1␣. Furthermore, IFN␥ induced 2-fold and 3-fold increases in chondrocyte death in WT controls and Fc␥RIII ؊/؊ mice, respectively. Notably, VDIPEN expression also remained high in Fc␥RIII ؊/؊ mice.Conclusion. IFN␥ bypasses the dependence on Fc␥RIII in the development of IC-mediated arthritis. Furthermore, both Fc␥RI and Fc␥RIII can mediate MMP-dependent cartilage matrix destruction.

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Section: Discussionmentioning

confidence: 80%

Joint inflammation and chondrocyte death become independent of Fcγ receptor type III by local overexpression of interferon‐γ during immune complex–mediated arthritis

Nabbe¹,

Boross²,

Holthuysen³

et al. 2005

Arthritis & Rheumatism

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“…OT-1 C57Bl/6J mice and Ly5.1 congenic mice were obtained from Jackson Lab, (Bar Harbor, ME, USA). C57Bl/6J FcgRI À / À mice, 23 FcgRI/IIIA/IV ('FcgRIIB-only'), 26 FcgRIII À / À mice, 22 FcgRIV À / À mice, 24 and FcgRI/IIB/III FceRI/II (5KO, also known as 'FcgRIV-only') mice 25 Tumor-infiltrating lymphocytes analyses. At indicated time points, tumors were harvested, cut into small pieces and digested in Liberase TM 25 mg/ml (Roche, Boulogne Billancourt, France) and DNase I 150 U/ml (Calbiochem, Millipore, Molsheim, France) for 30 min at 37 1C.…”

Section: Methodsmentioning

confidence: 99%

“…FcgRs are broadly expressed on immune cells and encompass both activating, for example, FcgRI, III and IV (including the FcRg subunit), and inhibitory, for example, FcgRIIB and subtype complexes. 21 MCA205 OVA was inoculated into the mice genetically manipulated to lack specific FcRg subtypes, namely FcgRIII, 22 FcgRI, 23 FcgRIV, 24 as well as into 'FcgRIV only' mice (which lack FcgRI/IIB/III/FceRI/II genes) 25 or 'FcgRIIB only' mice (which lack the FcgRI/IIIA/IV genes). 26 Thus, anthracyclines similarly reduced tumor growth in these FcRg-deficient mice (Figures 5a-f), as it did in WT C57Bl6 controls (see above, Figure 2a).…”

Section: Contribution Of B-cell Responses After Chemotherapy D Hannanmentioning

confidence: 99%

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

et al. 2013

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Immunogenic cell death induced by cytotoxic compounds contributes to the success of selected chemotherapies by eliciting a protective anticancer immune response, which is mediated by CD4 þ and CD8 þ T cells producing interferon-c. In many instances, cancer progression is associated with high titers of tumor-specific antibodies, which become detectable in the serum, but whose functional relevance is elusive. Here, we explored the role of humoral immune responses in the anticancer efficacy of anthracyclines. Chemotherapy reduced the number of tumor-infiltrating B cells, and failed to promote humoral responses against immunodominant tumor antigens. Although anthracycline-based anticancer chemotherapies failed in T cell-deficient mice, they successfully reduced the growth of cancers developing in mice lacking B lymphocytes (due to the injection of a B-celldepleting anti-CD20 antibody), immunoglobulins (Igs) or Ig receptors (Fc receptor) due to genetic manipulations. These results suggest that the humoral arm of antitumor immunity is dispensable for the immune-dependent therapeutic effect of anthracyclines against mouse sarcoma. In addition, we show here that the titers of IgA and IgG antibodies directed against an autoantigen appearing at the cell surface of tumor cells post chemotherapy (calreticulin, CRT) did not significantly increase in patients treated with anthracyclines, and that anti-CRT antibodies had no prognostic or predictive significance. Collectively, our data indicate that humoral anticancer immune responses differ from cellular responses in, thus far, that they do not contribute to the success of anthracycline-mediated anticancer therapies in human breast cancers and mouse sarcomas.

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“…In contrast to HVs, a significant expression of CD64 [a wellknown marker for phagocytosis (30,31)] was found in CLL monocytes (Fig. 2B).…”

Section: Lps Ex Vivo Challenge Of Isolated Monocytes Revealed An Et Smentioning

confidence: 97%

“…In addition to a potent phagocytic function, CD64 is associated with a low Ag-presentation capacity (15,30,31). When we studied the cell surface levels of two important isotypes of MHC class II (HLA-DR and HLA-DQ) by flow cytometry in patients with CLL, they showed a significantly reduced expression after LPS challenge (Fig.…”

Section: Lps Ex Vivo Challenge Of Isolated Monocytes Revealed An Et Smentioning

confidence: 99%

Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance

Jurado-Camino

Esteban-Burgos

Hernández-Jiménez

et al. 2015

The Journal of Immunology

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Infections are a significant cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections is multifactorial and includes hypogammaglobulinemia, conventional therapy with alkylating drugs, and recently, purine analogs and mAb-associated T cells. Patients without these risk factors also suffer from infections, although the mechanism remains unknown. In a cohort of 70 patients with CLL, we demonstrated that their monocytes were locked into a refractory state and were unable to mount a classic inflammatory response to pathogens. In addition, they exhibited the primary features of endotoxin tolerance, including low cytokine production, high phagocytic activity, and impaired Ag presentation. The involvement of miR-146a in this phenomenon was suspected. We found miR-146a target genes, such as IRAK1 and TRAF6, were manifestly downregulated. Our study provides a new explanation for infections in patients with CLL and describes a cross-tolerance between endotoxins and tumors.

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FcγRI (CD64) Contributes Substantially to Severity of Arthritis, Hypersensitivity Responses, and Protection from Bacterial Infection

Cited by 280 publications

References 34 publications

Joint inflammation and chondrocyte death become independent of Fcγ receptor type III by local overexpression of interferon‐γ during immune complex–mediated arthritis

Joint inflammation and chondrocyte death become independent of Fcγ receptor type III by local overexpression of interferon‐γ during immune complex–mediated arthritis

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

Chronic Lymphocytic Leukemia: A Paradigm of Innate Immune Cross-Tolerance

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