The Experts below are selected from a list of 17304 Experts worldwide ranked by ideXlab platform
Jeffrey V. Ravetch - One of the best experts on this subject based on the ideXlab platform.
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the role of igg Fc Receptors in antibody dependent enhancement
Nature Reviews Immunology, 2020Co-Authors: Stylianos Bournazos, Aaron Gupta, Jeffrey V. RavetchAbstract:Antibody-dependent enhancement (ADE) is a mechanism by which the pathogenesis of certain viral infections is enhanced in the presence of sub-neutralizing or cross-reactive non-neutralizing antiviral antibodies. In vitro modelling of ADE has attributed enhanced pathogenesis to Fcγ receptor (FcγR)-mediated viral entry, rather than canonical viral receptor-mediated entry. However, the putative FcγR-dependent mechanisms of ADE overlap with the role of these Receptors in mediating antiviral protection in various viral infections, necessitating a detailed understanding of how this diverse family of Receptors functions in protection and pathogenesis. Here, we discuss the diversity of immune responses mediated upon FcγR engagement and review the available experimental evidence supporting the role of FcγRs in antiviral protection and pathogenesis through ADE. We explore FcγR engagement in the context of a range of different viral infections, including dengue virus and SARS-CoV, and consider ADE in the context of the ongoing SARS-CoV-2 pandemic.
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Type I and type II Fc Receptors regulate innate and adaptive immunity
Nature Immunology, 2014Co-Authors: Andrew Pincetic, Stylianos Bournazos, David J Dilillo, Jad Maamary, Taia T Wang, Rony Dahan, Benjamin-maximillian Fiebiger, Jeffrey V. RavetchAbstract:Antibodies produced in response to a foreign antigen are characterized by polyclonality, not only in the diverse epitopes to which their variable domains bind but also in the various effector molecules to which their constant regions (Fc domains) engage. Thus, the antibody's Fc domain mediates diverse effector activities by engaging two distinct classes of Fc Receptors (type I and type II) on the basis of the two dominant conformational states that the Fc domain may adopt. These conformational states are regulated by the differences among antibody subclasses in their amino acid sequence and by the complex, biantennary Fc-associated N -linked glycan. Here we discuss the diverse downstream proinflammatory, anti-inflammatory and immunomodulatory consequences of the engagement of type I and type II Fc Receptors in the context of infectious, autoimmune, and neoplastic disorders.
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aglycosylated immunoglobulin g1 variants productively engage activating Fc Receptors
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Stephen L Sazinsky, Jeffrey V. Ravetch, Rene G Ott, Nathaniel W Silver, Bruce Tidor, Dane K WittrupAbstract:Immunoglobulin G plays a vital role in adaptive immunity and antibody-based therapy through engagement of its Fc region by the Fcγ Receptors (FcγRs) on immune cells. In addition to specific protein-protein contacts, N-linked glycosylation of the IgG Fc has been thought to be essential for the recognition of Fc by FcγR. This requirement for the N-linked glycan has limited biomanufacture of therapeutic antibodies by restricting it to mammalian expression systems. We report here aglycosylated Fc domain variants that maintain engagement to FcγRs, both in vitro and in vivo, demonstrating that Fc glycosylation is not strictly required for the activation of immune cells by IgG. These variants provide insight into how the N-linked glycan is used biologically in the recognition of Fc by FcγRs, as well as represent a step toward the production in alternative expression systems of antibody-based therapeutics capable of eliciting immune effector functions.
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agalactosylated igg antibodies depend on cellular Fc Receptors for in vivo activity
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Falk Nimmerjahn, Robert M Anthony, Jeffrey V. RavetchAbstract:IgG antibodies are glycoproteins containing a branched sugar moiety attached to the asparagine 297 residue in the antibody constant region (Fc). This glycan is essential for maintaining a functional Fc structure, which is a prerequisite for antibody-mediated effector functions, such as the interaction with cellular Fc Receptors or the complement component C1q. Variations in the composition of the sugar moiety can dramatically influence antibody activity. Moreover, humans and mice with autoimmune disorders, such as rheumatoid arthritis, have altered IgG glycosylation patterns with increased levels of antibodies lacking terminal sialic acid and galactose residues (IgG-G0). There is great interest in understanding whether this altered glycosylation pattern influences antibody-mediated effector functions. In vitro studies have suggested that IgG-G0 antibodies gain the capacity to activate the complement pathway via mannose-binding lectin (MBL), which could contribute to antibody-mediated inflammation. We have analyzed the activity of IgG-G0 antibodies in mice with a genetic deletion of MBL (MBL-null mice) and demonstrate that IgG-G0 antibodies are unimpaired in MBL-null mice. In contrast, the activity of these antibody glycovariants is fully dependent on the presence of activating Fc Receptors.
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antibodies Fc Receptors and cancer
Current Opinion in Immunology, 2007Co-Authors: Falk Nimmerjahn, Jeffrey V. RavetchAbstract:Since the first report of the successful use of a monoclonal antibody for the treatment of human B cell lymphoma in 1982, several antibodies have become incorporated into standard treatment protocols for cancer. One of the most important factors that determine antibody activity in vivo is the efficient interaction with cellular Fc-Receptors on innate immune effector cells. It has become clear that the outcome of this interaction is influenced by several factors, such as the antibody isotype-specific affinity to activating and inhibitory Receptors, the level of inhibitory FcgammaRIIB expression, and the composition of the sugar side chain attached to the antibody Fc-portion. These novel insights into antibody FcR interactions might be useful to produce the next generation of improved immunotherapeutic molecules.
Masao Ono - One of the best experts on this subject based on the ideXlab platform.
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Modulation of Immunoglobulin (Ig)E-mediated Systemic Anaphylaxis by Low-Affinity Fc Receptors for IgG
The Journal of experimental medicine, 1999Co-Authors: Azusa Ujike, Jeffrey V. Ravetch, Masao Ono, Yoko Ishikawa, Takae Yuasa, Tadashi Yoshino, Manabu Fukumoto, Toshiyuki TakaiAbstract:It is widely accepted that immunoglobulin (Ig)E triggers immediate hypersensitivity responses by activating a cognate high-affinity receptor, FceRI, leading to mast cell degranulation with release of vasoactive and proinflammatory mediators. This apparent specificity, however, is complicated by the ability of IgE to bind with low affinity to Fc Receptors for IgG, FcγRII and III. We have addressed the in vivo significance of this interaction by studying IgE-mediated passive systemic anaphylaxis in FcγR-deficient mice. Mice deficient in the inhibitory receptor for IgG, FcγRIIB, display enhanced IgE-mediated anaphylactic responses, whereas mice deficient in an IgG activation receptor, FcγRIII, display a corresponding attenuation of IgE-mediated responses. Thus, in addition to modulating IgG-triggered hypersensitivity responses, FcγRII and III on mast cells are potent regulators of IgE-mediated responses and reveal the existence of a regulatory pathway for IgE triggering of effector cells through IgG Fc Receptors that could contribute to the etiology of the atopic response.
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modulation of immune complex induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc Receptors
Journal of Experimental Medicine, 1999Co-Authors: Raphael Clynes, Masao Ono, Toshiyuki Takai, Jay S Maizes, Rodolphe Guinamard, Jeffrey V. RavetchAbstract:Autoantibodies and immune complexes are major pathogenic factors in autoimmune injury, responsible for initiation of the inflammatory cascade and its resulting tissue damage. This activation results from the interaction of immunoglobulin (Ig)G Fc Receptors containing an activation motif (ITAM) with immune complexes (ICs) and cytotoxic autoantibodies which initiates and propagates an inflammatory response. In vitro, this pathway can be interrupted by coligation to FcγRIIB, an IgG Fc receptor containing an inhibitory motif (ITIM). In this report, we describe the in vivo consequences of FcγRII deficiency in the inflammatory response using a mouse model of IC alveolitis. At subthreshold concentrations of ICs that fail to elicit inflammatory responses in wild-type mice, FcγRII-deficient mice developed robust inflammatory responses characterized by increased hemorrhage, edema, and neutrophil infiltration. Bronchoalveolar fluids from FcγRII−/− stimulated mice contain higher levels of tumor necrosis factor and chemotactic activity, suggesting that FcγRII deficiency lowers the threshold of IC stimulation of resident cells such as the alveolar macrophage. In contrast, complement- and complement receptor–deficient mice develop normal inflammatory responses to suprathreshold levels of ICs, while FcRγ−/− mice are completely protected from inflammatory injury. An inhibitory role for FcγRII on macrophages is demonstrated by analysis of FcγRII−/− macrophages which show greater phagocytic and calcium flux responses upon FcγRIII engagement. These data reveal contrasting roles for the cellular Receptors for IgG on inflammatory cells, providing a regulatory mechanism for setting thresholds for IC sensitivity based on the ratio of ITIM to ITAM FcγR expression. Exploiting the FcγRII inhibitory pathway could thus provide a new therapeutic approach for modulating antibody-triggered inflammation.
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role of the inositol phosphatase ship in negative regulation of the immune system by the receptor feγriib
Nature, 1996Co-Authors: Jeffrey V. Ravetch, Masao Ono, Silvia Olland, Paul TempsAbstract:IMMUNE complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc Receptors (FcRs) such as FcΣRI or FcγRIII (ref. 1). On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc Receptors, a consequence of coligation of the B-cell antigen receptor or FcΣRI, respectively, and the inhibitory receptor FcγRIIB. Here we show that inhibitory signalling by FcγRIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of FcγRIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P3 and inositol(l,3,4,5)P4, suggests a mechanism by which FcγRIIB can inhibit calcium influx and downstream responses triggered by immune Receptors.
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role of the inositol phosphatase ship in negative regulation of the immune system by the receptor feγriib
Nature, 1996Co-Authors: Masao Ono, Jeffrey V. Ravetch, Silvia Bolland, Paul TempstAbstract:Immune complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc Receptors (FcRs) such as Fc(epsilon)RI or Fc(gamma)RIII. On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc Receptors, a consequence of coligation of the B-cell antigen receptor or Fc(epsilon)RI, respectively, and the inhibitory receptor Fc(gamma)RIIB. Here we show that inhibitory signalling by Fc(gamma)RIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of Fc(gamma)RIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P3 and inositol(1,3,4,5)P4, suggests a mechanism by which Fc(gamma)RIIB can inhibit calcium influx and downstream responses triggered by immune Receptors.
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role of the inositol phosphatase ship in negative regulation of the immune system by the receptor Fc gamma riib
Nature, 1996Co-Authors: Masao Ono, Jeffrey V. Ravetch, Silvia Bolland, Paul TempstAbstract:Immune complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc Receptors (FcRs) such as Fc(epsilon)RI or Fc(gamma)RIII. On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc Receptors, a consequence of coligation of the B-cell antigen receptor or Fc(epsilon)RI, respectively, and the inhibitory receptor Fc(gamma)RIIB. Here we show that inhibitory signalling by Fc(gamma)RIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of Fc(gamma)RIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P3 and inositol(1,3,4,5)P4, suggests a mechanism by which Fc(gamma)RIIB can inhibit calcium influx and downstream responses triggered by immune Receptors.
Silvia Bolland - One of the best experts on this subject based on the ideXlab platform.
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igg Fc Receptors
Annual Review of Immunology, 2001Co-Authors: Jeffrey V. Ravetch, Silvia BollandAbstract:Since the description of the first mouse knockout for an IgG Fc receptor seven years ago, considerable progress has been made in defining the in vivo functions of these Receptors in diverse biological systems. The role of activating FcγRs in providing a critical link between ligands and effector cells in type II and type III inflammation is now well established and has led to a fundamental revision of the significance of these Receptors in initiating cellular responses in host defense, in determining the efficacy of therapeutic antibodies, and in pathological autoimmune conditions. Considerable progress has been made in the last two years on the in vivo regulation of these responses, through the appreciation of the importance of balancing activation responses with inhibitory signaling. The inhibitory FcR functions in the maintenance of peripheral tolerance, in regulating the threshold of activation responses, and ultimately in terminating IgG mediated effector stimulation. The consequences of deleting the...
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role of the inositol phosphatase ship in negative regulation of the immune system by the receptor feγriib
Nature, 1996Co-Authors: Masao Ono, Jeffrey V. Ravetch, Silvia Bolland, Paul TempstAbstract:Immune complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc Receptors (FcRs) such as Fc(epsilon)RI or Fc(gamma)RIII. On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc Receptors, a consequence of coligation of the B-cell antigen receptor or Fc(epsilon)RI, respectively, and the inhibitory receptor Fc(gamma)RIIB. Here we show that inhibitory signalling by Fc(gamma)RIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of Fc(gamma)RIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P3 and inositol(1,3,4,5)P4, suggests a mechanism by which Fc(gamma)RIIB can inhibit calcium influx and downstream responses triggered by immune Receptors.
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role of the inositol phosphatase ship in negative regulation of the immune system by the receptor Fc gamma riib
Nature, 1996Co-Authors: Masao Ono, Jeffrey V. Ravetch, Silvia Bolland, Paul TempstAbstract:Immune complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc Receptors (FcRs) such as Fc(epsilon)RI or Fc(gamma)RIII. On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc Receptors, a consequence of coligation of the B-cell antigen receptor or Fc(epsilon)RI, respectively, and the inhibitory receptor Fc(gamma)RIIB. Here we show that inhibitory signalling by Fc(gamma)RIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of Fc(gamma)RIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P3 and inositol(1,3,4,5)P4, suggests a mechanism by which Fc(gamma)RIIB can inhibit calcium influx and downstream responses triggered by immune Receptors.
Jan G J Van De Winkel - One of the best experts on this subject based on the ideXlab platform.
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iga Fc Receptors
Annual Review of Immunology, 2003Co-Authors: Renato C Monteiro, Jan G J Van De WinkelAbstract:▪ Abstract The IgA receptor family comprises a number of surface Receptors including the polymeric Ig receptor involved in epithelial transport of IgA/IgM, the myeloid specific IgA Fc receptor (FcαRI or CD89), the Fcα/μR, and at least two alternative IgA Receptors. These are the asialoglycoprotein receptor and the transferrin receptor, which have been implicated in IgA catabolism, and tissue IgA deposition. In this reviewwe focus on the biology of FcαRI (CD89). FcαRI is expressed on neutrophils, eosinophils, monocytes/macrophages, dendritic cells, and Kupffer cells. This receptor represents a heterogeneously glycosylated transmembrane protein that binds both IgA subclasses with low affinity. A single gene encoding FcαRI has been isolated, which is located within the leukocyte receptor cluster on chromosome 19. The FcαRI α chain lacks canonical signal transduction domains but can associate with the FcR γ-chain that bears an activation motif (ITAM) in the cytoplasmic domain, allowing activatory functions. F...
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clinical significance of igg Fc Receptors and Fcγr directed immunotherapies
Immunology Today, 1997Co-Authors: Yashwant M Deo, Robert F Graziano, Roland Repp, Jan G J Van De WinkelAbstract:Fc Receptors for IgG (Fc gamma Rs) can trigger the inflammatory, cytotoxic and hypersensitivity functions of immune effector cells. Activation or deactivation of effector cells via Fc gamma Rs can be exploited to develop novel therapies for cancer, infectious diseases and autoimmune disorders. Initial results of clinical trials for several Fc gamma R-directed immunotherapies show the potential promise of this approach.
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human igg Fc Receptors
International Reviews of Immunology, 1997Co-Authors: I A F M Heijnen, Jan G J Van De WinkelAbstract:Human IgG Receptors constitute a family of glycoprotein complexes consisting of ligand-binding, and associated signaling chains. Three leukocyte classes (Fc gamma RI, II, and III) and one separate endothelial Fc gamma R class (FcRB) are defined which are expressed on hematopoietic and endothelial cells. Upon interaction with IgG, Fc gamma R initiate a plethora of signaling cascades involving receptor signaling motifs, and protein tyrosine kinases and phosphatases. These cascades ultimately culminate in activation or deactivation of effector cells, resulting in initiation or down-modulation of cellular processes. Recent evidence points to a crucial in vivo role of Fc gamma R in both initiation and regulation of inflammatory and cytotoxic responses. These Fc gamma R-mediated immune responses can be exploited to develop novel immunotherapies.
Toshiyuki Takai - One of the best experts on this subject based on the ideXlab platform.
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Role of Fc Receptors as a Therapeutic Target
Inflammation & allergy drug targets, 2009Co-Authors: Atsuhiro Masuda, Toshiyuki Takai, Masaru Yoshida, Hideyuki Shiomi, Yoshinori Morita, Hiromu Kutsumi, Hideto Inokuchi, Shigeto Mizuno, Akira Nakamura, Richard S. BlumbergAbstract:It has been forty years since the discovery of Fc Receptors and their function. Fc Receptors include the IgG Receptors (FcγR), high-affinity IgE receptor (FcηRI), IgA and IgA/IgM Receptors, and neonatal Fc receptor for IgG (FcRn). In particular, the FcγRs have been well known to play an important role in many biologic processes including those associated with the response to infection and cancer as well as in the pathogenesis of immune-mediated diseases. Both positive and negative regulatory function has ascribed to Fc Receptors and FcγRs in particular which serve to establish a threshold for immune cell activation. In other cases, Fc Receptors such as FcRn possess a novel structure and function by playing a major role in the transport of IgG across polarized epithelial barriers at mucosal surfaces and in the regulation of IgG halflife. These diverse functions highlight the potential effectiveness of targeting Fc Receptors for therapeutic purposes. This review summarizes new information available in the therapeutic applications of this biology.
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Fc Receptors and Their Role in Immune Regulation and Autoimmunity
Journal of Clinical Immunology, 2005Co-Authors: Toshiyuki TakaiAbstract:The activation threshold of cells in the immune system is often tuned by cell surface molecules. The Fc Receptors expressed on various hematopoietic cells constitute critical elements for activating or downmodulating immune responses and combines humoral and cell-mediated immunity. Thus, Fc Receptors are the intelligent sensors of the immune status in the individual. However, impaired regulation by Fc Receptors will lead to unresponsiveness or hyperreactivity to foreign as well as self-antigens. Murine models for autoimmune disease indicate the indispensable roles of the inhibitory Fc receptor in the suppression of such disorders, whereas activating-type FcRs are crucial for the onset and exacerbation of the disease. The development of many autoimmune diseases in humans may be caused by impairment of the human Fc receptor regulatory system. This review is aimed at providing a current overview of the mechanism of Fc receptor-based immune regulation and the possible scenario of how autoimmune disease might result from their dysfunction.
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roles of Fc Receptors in autoimmunity
Nature Reviews Immunology, 2002Co-Authors: Toshiyuki TakaiAbstract:The Receptors for the Fc of immunoglobulins, Fc Receptors (FcRs), link the humoral and cellular branches of the immune system, and they have important functions in the activation and down-modulation of immune responses. Balanced signalling through activating and inhibitory FcRs regulates the activity of various cells in the immune system. Recent work in animal models indicates that the development of many human autoimmune diseases might be caused by impairment of the FcR regulatory system. This review provides an overview of the mechanisms of FcR-based immune regulation and describes how autoimmune disease might result from its dysfunction.
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Modulation of Immunoglobulin (Ig)E-mediated Systemic Anaphylaxis by Low-Affinity Fc Receptors for IgG
The Journal of experimental medicine, 1999Co-Authors: Azusa Ujike, Jeffrey V. Ravetch, Masao Ono, Yoko Ishikawa, Takae Yuasa, Tadashi Yoshino, Manabu Fukumoto, Toshiyuki TakaiAbstract:It is widely accepted that immunoglobulin (Ig)E triggers immediate hypersensitivity responses by activating a cognate high-affinity receptor, FceRI, leading to mast cell degranulation with release of vasoactive and proinflammatory mediators. This apparent specificity, however, is complicated by the ability of IgE to bind with low affinity to Fc Receptors for IgG, FcγRII and III. We have addressed the in vivo significance of this interaction by studying IgE-mediated passive systemic anaphylaxis in FcγR-deficient mice. Mice deficient in the inhibitory receptor for IgG, FcγRIIB, display enhanced IgE-mediated anaphylactic responses, whereas mice deficient in an IgG activation receptor, FcγRIII, display a corresponding attenuation of IgE-mediated responses. Thus, in addition to modulating IgG-triggered hypersensitivity responses, FcγRII and III on mast cells are potent regulators of IgE-mediated responses and reveal the existence of a regulatory pathway for IgE triggering of effector cells through IgG Fc Receptors that could contribute to the etiology of the atopic response.
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modulation of immune complex induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc Receptors
Journal of Experimental Medicine, 1999Co-Authors: Raphael Clynes, Masao Ono, Toshiyuki Takai, Jay S Maizes, Rodolphe Guinamard, Jeffrey V. RavetchAbstract:Autoantibodies and immune complexes are major pathogenic factors in autoimmune injury, responsible for initiation of the inflammatory cascade and its resulting tissue damage. This activation results from the interaction of immunoglobulin (Ig)G Fc Receptors containing an activation motif (ITAM) with immune complexes (ICs) and cytotoxic autoantibodies which initiates and propagates an inflammatory response. In vitro, this pathway can be interrupted by coligation to FcγRIIB, an IgG Fc receptor containing an inhibitory motif (ITIM). In this report, we describe the in vivo consequences of FcγRII deficiency in the inflammatory response using a mouse model of IC alveolitis. At subthreshold concentrations of ICs that fail to elicit inflammatory responses in wild-type mice, FcγRII-deficient mice developed robust inflammatory responses characterized by increased hemorrhage, edema, and neutrophil infiltration. Bronchoalveolar fluids from FcγRII−/− stimulated mice contain higher levels of tumor necrosis factor and chemotactic activity, suggesting that FcγRII deficiency lowers the threshold of IC stimulation of resident cells such as the alveolar macrophage. In contrast, complement- and complement receptor–deficient mice develop normal inflammatory responses to suprathreshold levels of ICs, while FcRγ−/− mice are completely protected from inflammatory injury. An inhibitory role for FcγRII on macrophages is demonstrated by analysis of FcγRII−/− macrophages which show greater phagocytic and calcium flux responses upon FcγRIII engagement. These data reveal contrasting roles for the cellular Receptors for IgG on inflammatory cells, providing a regulatory mechanism for setting thresholds for IC sensitivity based on the ratio of ITIM to ITAM FcγR expression. Exploiting the FcγRII inhibitory pathway could thus provide a new therapeutic approach for modulating antibody-triggered inflammation.
