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P89 Novel mechanisms of immunomodulation by vitamin D and α-1-antitrypsin
  1. LV Rice1,
  2. S Dimeloe1,
  3. J Raynes2,
  4. A Gupta3,
  5. O Pfeffe1,
  6. D Richards1,
  7. Z Urry1,
  8. S Farooque1,
  9. P Ozegbe1,
  10. E Hornsby1,
  11. M Nyon4,
  12. I Haq5,
  13. J Irving5,
  14. J McDonnell1,
  15. S Saglani3,
  16. A Bush3,
  17. B Gooptu4,
  18. C Kemper6,
  19. C Hawrylowicz1
  1. 1MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, london, uk
  2. 2Immunology and Infection Department, London School of Hygiene and Tropical Medicine, LONDON, UK
  3. 3MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, Imperial College London, Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK
  4. 4Institute of Structural and Molecular Biology/Crystallography, Department of Biological Sciences, Birkbeck College, University of London, London, UK
  5. 5Cambridge Institute for Medical Research, University of Cambridge, MRC/Wellcome Trust Building, Cambridge, UK
  6. 6MRC Centre for Transplantation, Division of Transplantation Immunology and Mucosal Biology, King’s College London, Guy’s Hospital, London, UK

Abstract

Vitamin D deficiency/insufficiency has been associated with poor respiratory health and a predisposition to respiratory disease. Local activation of vitamin D in the airways is important for antimicrobial defenses and suppression of inflammatory responses via the generation of a tolerogenic immune environment. One of the most highly unregulated proteins by vitamin D in CD4+ T-cells is the serine protease inhibitor α-1-antitrypsin. In addition to controlling the pro-inflammatory effects of neutrophil elastase, α-1-antitrypsin also acts via other pathways as an immunomodulator. We have identified a novel axis of immune modulation by vitamin D; where α-1-antitrypsin is able to induce IL-10 production in PBMCs via an interaction with the complement component C3a. Our in vitro findings are supported by in vivo correlations of serum vitamin D, α-1-antitrypsin, C3a and IL-10 in the airways of both asthmatics and healthy controls from a paediatric cohort. We propose that vitamin D is an upstream regulator of the α-1-antitrypsin/C3a/IL-10 axis, providing attractive therapeutic options to promote tolerance in a range of inflammatory diseases.

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