Abstract
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 α-galactosylceramide (αGalCer), evidenced by an increase in the number of splenic dendritic cells, NKT cells, and germinal center plasmacytes. RA also differentially regulated αGalCer-induced cytokine expression, increasing IL-4 and decreasing IFNγ 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 32-41 |
| Number of pages | 10 |
| Journal | Immunobiology |
| Volume | 220 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2015 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Hematology
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All-trans-retinoic acid and CD38 ligation differentially regulate CD1d expression and α-galactosylceramide-induced immune responses. / Chen, Qiuyan; Ross, A. Catharine.
In: Immunobiology, Vol. 220, No. 1, 01.01.2015, p. 32-41.Research output: Contribution to journal › Article
TY - JOUR
T1 - All-trans-retinoic acid and CD38 ligation differentially regulate CD1d expression and α-galactosylceramide-induced immune responses
AU - Chen, Qiuyan
AU - Ross, A. Catharine
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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 α-galactosylceramide (αGalCer), evidenced by an increase in the number of splenic dendritic cells, NKT cells, and germinal center plasmacytes. RA also differentially regulated αGalCer-induced cytokine expression, increasing IL-4 and decreasing IFNγ 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.
AB - 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 α-galactosylceramide (αGalCer), evidenced by an increase in the number of splenic dendritic cells, NKT cells, and germinal center plasmacytes. RA also differentially regulated αGalCer-induced cytokine expression, increasing IL-4 and decreasing IFNγ 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.
UR - http://www.scopus.com/inward/record.url?scp=84979859111&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979859111&partnerID=8YFLogxK
U2 - 10.1016/j.imbio.2014.09.008
DO - 10.1016/j.imbio.2014.09.008
M3 - Article
C2 - 25248321
AN - SCOPUS:84979859111
VL - 220
SP - 32
EP - 41
JO - Immunobiology
JF - Immunobiology
SN - 0171-2985
IS - 1
ER -