1α,25-Dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells
- Sarah Dimeloe1,
- David F Richards1,
- Zoe L Urry1,
- Atul Gupta1,2,
- Victoria Stratigou1,
- Sophie Farooque1,
- Sejal Saglani2,
- Andrew Bush2,
- Catherine M Hawrylowicz1
- 1MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, Guy's Hospital, London, UK
- 2Department of Pediatric Respiratory Medicine, Imperial College and Royal Brompton Hospital, London, UK
- Correspondence to Professor Catherine M Hawrylowicz, Department of Asthma, Allergy and Respiratory Science, 5th Floor Tower Wing, Guy's Hospital, King's College London, London SE1 9RT, UK;
Contributors Experimental work was carried out by SD with contribution from DFR and VS. Adult respiratory tissue was sourced by SF. Material from in vivo studies was generated and generously provided by ZU. Paediatric bronchoalveolar lavage material was obtained and generously provided by AG, SS and AB. The manuscript was prepared by SD and CMH and all studies were conceived by CMH.
- Received 21 June 2011
- Accepted 13 January 2012
- Published Online First 14 February 2012
Background CD200, a cell-surface immunoglobulin-like molecule expressed by immune and stromal cells, dampens the pro-inflammatory activity of tissue-resident innate cells via its receptor, CD200R. This interaction appears critical for peripheral immune tolerance, particularly in the airways where excessive inflammation is undesirable. Vitamin D contributes to pulmonary health and promotes regulatory immune pathways, therefore its influence on CD200 and CD200R was investigated.
Methods CD200 and CD200R expression were assessed by qPCR and immunoreactivity of human lymphoid, myeloid and epithelial cells following 1α,25-dihydroxyvitamin D3 (1α,25VitD3) exposure in vitro and in peripheral T cells following 1α,25VitD3 oral ingestion in vivo. The effect of 1α25VitD3 was also assessed in human airway-resident cells.
Results 1α25VitD3 potently upregulated CD200 on peripheral human CD4+ T cells in vitro, and in vivo there was a trend towards upregulation in healthy, but not asthmatic individuals. CD200R expression was not modulated in any cells studied. CD200 induction was observed to a lesser extent in CD8+ T cells and not in B cells or airway epithelium. T cells isolated from the human airway also responded strongly to 1α25VitD3 to upregulate CD200.
Conclusions The capacity of 1α,25-dihydroxyvitamin D3 to induce CD200 expression by peripheral and respiratory tract T cells identifies an additional pathway via which vitamin D can restrain inflammation in the airways to maintain respiratory health.
- Allergic lung disease
- α1 antitrypsin deficiency
- asthma epidemiology
- asthma mechanisms
- innate immunity
- paediatric asthma
- lymphocyte biology
- airway epithelium
- eosinophil biology
- lymphocyte biology
- macrophage biology
- neutrophil biology
- asthma guidelines
- cystic fibrosis
- exhaled airway markers
- lung physiology
- paediatric lung disease
Funding SD is the recipient of a Medical Research Council (MRC) funded PhD Studentship through the MRC & Asthma UK Centre for Allergic Mechanisms of Asthma. At the time of this study ZU was funded by an MRC CASE PhD studentship, held in association with Novartis Institute for Biomedical Research. VS is the recipient of an MRC Industrial Collaborative PhD studentship held in association with Novartis, Horsham, UK. AG is the recipient of a British Medical Association James Trust Fellowship. CH acknowledges financial and technical support from the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London.
Competing interests None to declare.
Ethics approval Guys Hospital Ethics Committee, Royal Brompton and Harefield NHS Trust Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.