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Intravenous immunoglobulin-mediated expansion of regulatory T cells in autoimmune patients is associated with increased prostaglandin E2 levels in the circulation

Cellular & Molecular Immunology volume 12, pages 650–652 (2015)Cite this article

CD4+FoxP3+ regulatory T cells (Tregs) are immunosuppressive cells that are critical for immune tolerance. Several studies have demonstrated that one of the anti-inflammatory mechanisms of action of intravenous immunoglobulin (IVIg) involves the expansion of Tregs. Recently, we demonstrated that IVIg-mediated Treg expansion involves the cyclooxygenase-2 (COX-2)-dependent induction of prostaglandin E2 (PGE2) in human dendritic cells (DCs). However, the validity of these findings in autoimmune patients is lacking. In this report, we demonstrate that the IVIg-mediated expansion of Tregs in autoimmune patients is associated with increased levels of circulatory PGE2. Due to its immunomodulatory effects on various immune cells, this increase in PGE2 represents one of the pathways by which IVIg exerts anti-inflammatory effects.

IVIg is a therapeutic preparation of normal circulating IgG obtained from the pooled plasma of many healthy donors. Currently, high-dose IVIg therapy (1–2 g/kg body weight) is used in the treatment of diverse autoimmune and inflammatory conditions, such as Guillain–Barré syndrome (GBS), Kawasaki disease, idiopathic thrombocytopenic purpura and inflammatory myositis.1 The beneficial effects of IVIg are mediated by numerous mutually non-exclusive cellular and molecular mechanisms. These mechanisms indirectly suggest the functions of circulating IgG in the maintenance of immune homeostasis. The proposed mechanisms of IVIg include the following: inhibiting the activation of innate immune cells, such as DCs, macrophages, monocytes and neutrophils; suppressing pathogenic Th1 and Th17 subsets and reciprocally expanding CD4+FoxP3+ Tregs; inhibiting inflammatory cytokines and enhancing anti-inflammatory molecules; blocking complement activation; modulating B-cell functions; and neutralizing pathogenic autoantibodies.2,3

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Acknowledgements

This work was supported by the Institut National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie, Université Paris Descartes (SVK and JB); the Centre National de la Recherche Scientifique (SVK), the European Community's Seventh Framework Programme [FP7/2007–2013] under grant agreement 260338 ALLFUN (JB); the Indian Institute of Science, the Department of Biotechnology, the Department of Science and Technology, Council for Scientific and Industrial Research (KNB); Coopération INSERM-ICMR-AO 2009/2010 (KNB and JB) and fellowships from INSERM-ICMR, the Council for Scientific and Industrial Research (JT) and Journées de Neurologie de Langue Française (MR).

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale, Paris, France

    Mohan S Maddur, Jamma Trinath, Magalie Rabin, Srini V Kaveri & Jagadeesh Bayry

  2. Centre de Recherche des Cordeliers, Equipe - Immunopathology and Therapeutic Immunointervention, Paris, France

    Mohan S Maddur, Magalie Rabin, Srini V Kaveri & Jagadeesh Bayry

  3. Sorbonne Universités - UPMC Univ Paris 6, Paris, France

    Mohan S Maddur, Magalie Rabin, Srini V Kaveri & Jagadeesh Bayry

  4. Université Paris Descartes, Paris, France

    Mohan S Maddur, Srini V Kaveri & Jagadeesh Bayry

  5. Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India

    Jamma Trinath & Kithiganahalli N Balaji

  6. Centre de Référence ‘Neuropathies Périphériques Rares' et Service de Neurologie, Hôpital Universitaire Limoges, Limoges, France

    Magalie Rabin, Jean-Michel Vallat & Laurent Magy

  7. Réanimation Neurologique, Neurologie 1, Hôpital de la Pitié-Salpêtrière, Paris, France

    Francis Bolgert & Moneger Guy

  8. International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France - Indian Council of Medical Research, India), National Institute of Immunohaematology, Mumbai, India

    Srini V Kaveri & Jagadeesh Bayry

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  1. Mohan S Maddur
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Correspondence to Srini V Kaveri or Jagadeesh Bayry.

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This work is partially supported by financial support from CSL Behring, France.

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Maddur, M., Trinath, J., Rabin, M. et al. Intravenous immunoglobulin-mediated expansion of regulatory T cells in autoimmune patients is associated with increased prostaglandin E2 levels in the circulation. Cell Mol Immunol 12, 650–652 (2015). https://doi.org/10.1038/cmi.2014.117

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  • DOI: https://doi.org/10.1038/cmi.2014.117

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