1α,25-dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells

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 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25VitD3) exposure in vitro and in peripheral T cells following 1 alpha,25VitD3 oral ingestion in vivo. The effect of 1 alpha 25VitD3 was also assessed in human airway-resident cells.

Results 
1 alpha 25VitD3 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 1 alpha 25VitD3 to upregulate CD200.

Conclusions 
The capacity of 1 alpha,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.