While most work has focused on CD1 proteins as antigen presenting molecules, CD1 proteins also serve as defining features of human dendritic cell (DC) differentiation. Prior gene expression studies in response to bacterial factors highlighted opposing regulation of group 1 CD1 (CD1a, CD1b and CD1c) and group 2 (CD1d), where CD1a, CD1b and CD1c were thought to be concomitantly upregulated and undertake parallel functions in presenting foreign lipid antigens to T cells. CD1a expression in monocyte derived DCs was previously shown to be inhibited by all-trans-retinoic-acid, a precursor of which is vitamin A. Interestingly, vitamin A deficiency was recently reported to be a strong predictor of progression to active tuberculosis in patients in Peru, and thus providing a previously unknown perspective on the role of a common nutrient in tuberculosis outcomes. We hypothesized that risk of tuberculosis progression can be partly mediated by vitamin A effects on DC maturation, tracked by upregulation of CD1 proteins.

We used multi-parameter flow cytometry to broadly determine expression patterns of CD1 and other markers on monocytes differentiated with IL-4 and GM-CSF. CD1c and HLA-DR were almost universally expressed on these cultured DCs by the second day. Subsequently, DCs upregulated CD1b expression by day 3, and fully differentiated into CD1a⁺CD1b⁺ cells by day 6. All-trans-retinoic-acid selectively inhibited transition from the CD1a^-CD1b⁺ into CD1a⁺CD1b⁺ DC stages in a dose-dependent manner. Conversely, chemical inhibition of all-trans-retinoic-acid reversed this effect. These results demonstrate orchestrated step-wise up-regulation of CD1 proteins during in vitro differentiation of DCs, leading to ongoing efforts to define transcriptional factors that control CD1 protein expression and DC differentiation. These findings will shed light on how a common micronutrient regulates CD1 expression as a proxy for differentiation of DCs, which are currently used as agents of immunotherapy and vaccination.