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Role of FcγRIIIA (CD16) in IVIg-Mediated Anti-Inflammatory Function

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Abstract

The mechanism for anti-inflammatory action of intravenous immunoglobulin (IVIg) in the treatment of autoimmune and inflammatory diseases involves IgG Fc receptors (FcγR). Although the inhibitory FcγRIIB plays an important role in IVIg action, FcγRIIIA has recently been identified as another major anti-inflammatory actor. Interaction of FcγRIIIA with uncomplexed IgG1 or IVIg, or with bivalent anti-FcγRIII F(ab’)2 dampened calcium responses, ROS production, endocytosis and phagocytosis, induced by heterologous activating receptors. This inhibitory action required the inhibitory configuration of the ITAM motif (ITAMi) present within the FcγRIII-associated FcRγ subunit. This allowed SHP-1 recruitment and formation of intracellular inhibisome clusters containing FcγRIII and the targeted activating receptor. Therefore, IVIg functionally interact with FcγRIIIA inducing ITAMi signaling which can prevent development of autoimmune and inflammatory disorders independently of FcγRIIB. This new mechanism of action for IVIg reveals a therapeutic potential for FcγRIIIA targeting in inflammatory diseases.

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Acknowledgments

The authors thank Julien Claver for help with figures. This work was supported in part by grants from Agence Nationale de la Recherche (ANR grants MIEN-2009 and BLANC International-2012) and from the LabEx Inflamex. S.B.M. was supported by a grant from the French Foundation ARC (PDF20100601037).

Conflict of Interest Disclosure

The authors declare no competing financial interests.

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Author notes

  1. Meryem Aloulou

    Present address: INSERM U1043–CNRS Unité Mixte de Recherche 5282, Centre de Physiopathologie Toulouse-Purpan, Université Toulouse III, Toulouse, France

Authors and Affiliations

  1. Inserm, U1149, Centre de Recherche sur l’Inflammation, Paris, France

    Sanae Ben Mkaddem, Meryem Aloulou, Marc Benhamou & Renato C. Monteiro

  2. CNRS ERL8252, Paris, France

    Sanae Ben Mkaddem, Meryem Aloulou, Marc Benhamou & Renato C. Monteiro

  3. Sorbonne Paris Cité, Laboratoire d’Excellence Inflamex, Faculté de Médecine, Site Xavier Bichat, Université Paris Diderot, Paris, France

    Sanae Ben Mkaddem, Meryem Aloulou, Marc Benhamou & Renato C. Monteiro

  4. Laboratoire Dysfonctionnements Immunitaires, AP-HP, Hôpital Bichat, Paris, France

    Renato C. Monteiro

  5. INSERM UMR 1149, Faculté de Médecine Paris Diderot – Site Xavier Bichat - 16, Rue Henri Huchard, Paris Cedex 18, F-75018, France

    Renato C. Monteiro

Authors
  1. Sanae Ben Mkaddem
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  2. Meryem Aloulou
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  3. Marc Benhamou
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  4. Renato C. Monteiro
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Correspondence to Renato C. Monteiro.

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Ben Mkaddem, S., Aloulou, M., Benhamou, M. et al. Role of FcγRIIIA (CD16) in IVIg-Mediated Anti-Inflammatory Function. J Clin Immunol 34 (Suppl 1), 46–50 (2014). https://doi.org/10.1007/s10875-014-0031-6

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  • DOI: https://doi.org/10.1007/s10875-014-0031-6

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