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A pivotal role for antigen-presenting cells overexpressing SOCS3 in controlling invariant NKT cell responses during collagen-induced arthritis
  1. Sharon Veenbergen1,
  2. Miranda B Bennink1,
  3. Alsya J Affandi1,
  4. Natacha Bessis2,
  5. Jérôme Biton2,
  6. Onno J Arntz1,
  7. Wim B van den Berg1,
  8. Fons A J van de Loo1
  1. 1Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  2. 2EA4222, Physiology and Biotherapies of Rheumatoid Arthritis, University of Paris, Paris, Bobigny, France
  1. Correspondence to F A J van de Loo, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein 26–28, 6500 HB Nijmegen, The Netherlands; a.vandeLoo{at}reuma.umcn.nl

Abstract

Objective Suppressor of cytokine signalling (SOCS) proteins constitute a class of intracellular proteins that are key physiological regulators of immune cell function. It has previously been shown that antigen-presenting cells (APCs) overexpressing SOCS3 steer T helper immune responses and protect against experimental arthritis. A study was undertaken to investigate the contribution of SOCS3 in regulating invariant natural killer T (iNKT) cell responses during collagen-induced arthritis (CIA).

Methods DBA/1 mice were immunised with type II collagen and adenoviruses encoding SOCS3 were administered intravenously before the clinical onset of arthritis. Murine APCs overexpressing SOCS3 were co-cultured with an iNKT cell hybridoma and interleukin 2 (IL-2) release was measured by Luminex multi-analyte technology. The frequency and activation of primary iNKT cells was assessed by flow cytometry. Murine APCs were analysed for cytokine and CD1d expression following viral SOCS3 gene transfer.

Results Viral overexpression of SOCS3 in APCs resulted in reduced activation of the iNKT cell hybridoma. Importantly, during initiation of CIA, adenovirus-mediated overexpression of SOCS3 in hepatic and splenic APCs inhibited iNKT cell expansion in both organs. The iNKT cell population from SOCS3-treated mice showed low expression of the early activation marker CD69 and primary liver iNKT cells produced less interferon γ and IL-4 upon α-galactosylceramide stimulation. No differences in CD1d surface expression were observed, but SOCS3-transduced APCs produced decreased levels of proinflammatory cytokines and increased levels of IL-10.

Conclusion These results demonstrate a critical role for SOCS3 in controlling the immunostimulatory capacities of APCs, which has direct implications for the effector function of iNKT cells during arthritis.

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Footnotes

  • Funding This study was financially supported by the Dutch Arthritis Association (Grant Number 01-1-304) and Radboud University Nijmegen Medical Centre. FAJvdL is supported by the Dutch Organization for Scientific Research (Grant Number 917.46.363).

  • Competing interest None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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