All-trans-retinoic acid and CD38 ligation differentially regulate CD1d expression and alpha-galactosylceramide-induced immune responses

作者：Chen Qiuyan; Ross A Catharine^*

来源：Immunobiology, 2015, 220(1): 32-41.

DOI：10.1016/j.imbio.2014.09.008

• alpha-Galactosylceramide
• CD1d
• CD38
• Retinoic acid
• NKT cell
• IL-4 production
• IFN gamma production

The MHC class-I like molecule CD1d presents glycolipid antigens and thereby activates invariant natural killer-T (NKT) cells. However, little is understood regarding the regulation of its expression. All-trans-retinoic acid (RA) and CD38, which is itself a target of RA, both independently regulate the differentiation of antigen presenting cells. In the current study, we treated human THP-1 cells and murine splenic cells with RA, with and without antibody-mediated ligation of cell-surface CD38. Whereas a physiological concentration (20 nM) of RA alone rapidly and markedly increased CD1d protein in THP-1 cells, there was a marked synergy between RA and ligation of CD38 with antibody to CD38. Moreover, RA and CD38 ligation differentially regulated CD1d protein distribution between the cell surface and intracellular compartments, as, whereas RA mainly increased intracellular CD1d protein, ligation of CD38 increased CD1d protein both at the cell surface and intracellularly. By confocal microscopy, CD1d was located close to the plasma membrane but only partially overlapped with LAMP1, a late endosomes/lysosomal marker. Furthermore, RA and/or CD38 ligation increased splenocyte proliferation and differentiation after treatment with the CD1 ligand alpha-galactosylceramide (alpha GalCer), evidenced by an increase in the number of splenic dendritic cells, NKT cells, and germinal center plasmacytes. RA also differentially regulated alpha GalCer-induced cytokine expression, increasing IL-4 and decreasing IFN gamma production by total spleen cells and the NKT cell population. Our results indicate a previously unknown mechanism in which RA and CD38 differentially yet cooperatively regulate CD1d expression and antigen-presenting function, which could be important for the enhancement of immunity.

• 出版日期2015-1