Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells.
Publication/Presentation Date
9-23-2013
Abstract
Dendritic cells (DCs) comprise distinct populations with specialized immune-regulatory functions. However, the environmental factors that determine the differentiation of these subsets remain poorly defined. Here, we report that retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC (precursor of DC)-derived splenic CD11b(+)CD8α(-)Esam(high) DCs and the developmentally related CD11b(+)CD103(+) subset within the gut. Whereas mice deprived of RA signaling significantly lost both of these populations, neither pre-DC-derived CD11b(-)CD8α(+) and CD11b(-)CD103(+) nor monocyte-derived CD11b(+)CD8α(-)Esam(low) or CD11b(+)CD103(-) DC populations were deficient. In fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts resulted in near complete conversion of these cells into the CD11b(+)CD8α(-) subset, whereas transfer into vitamin A-deficient (VAD) hosts caused diversion to the CD11b(-)CD8α(+) lineage. As vitamin A is an essential nutrient, we evaluated retinoid levels in mice and humans after radiation-induced mucosal injury and found this conditioning led to an acute VAD state. Consequently, radiation led to a selective loss of both RA-dependent DC subsets and impaired class II-restricted auto and antitumor immunity that could be rescued by supplemental RA. These findings establish a critical role for RA in regulating the homeostasis of pre-DC-derived DC subsets and have implications for the management of patients with immune deficiencies resulting from malnutrition and irradiation.
Volume
210
Issue
10
First Page
1961
Last Page
1976
ISSN
1540-9538
Published In/Presented At
Klebanoff, C. A., Spencer, S. P., Torabi-Parizi, P., Grainger, J. R., Roychoudhuri, R., Ji, Y., Sukumar, M., Muranski, P., Scott, C. D., Hall, J. A., Ferreyra, G. A., Leonardi, A. J., Borman, Z. A., Wang, J., Palmer, D. C., Wilhelm, C., Cai, R., Sun, J., Napoli, J. L., Danner, R. L., … Restifo, N. P. (2013). Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. The Journal of experimental medicine, 210(10), 1961–1976. https://doi.org/10.1084/jem.20122508
Disciplines
Medicine and Health Sciences
PubMedID
23999499
Department(s)
Department of Medicine
Document Type
Article