Back to Search
Start Over
Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells
- Source :
- The Journal of experimental medicine, vol 210, iss 10
- Publication Year :
- 2013
- Publisher :
- eScholarship, University of California, 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.
- Subjects :
- Cell Survival
1.1 Normal biological development and functioning
Retinoic Acid
Immunology
Tretinoin
Medical and Health Sciences
Immunophenotyping
Vaccine Related
Mice
Underpinning research
Biodefense
Neoplasms
Receptors
Animals
Humans
Homeostasis
Intestinal Mucosa
Vitamin A
Nutrition
Cell Proliferation
Prevention
Inflammatory and immune system
Histocompatibility Antigens Class II
Cell Differentiation
Dendritic Cells
Intestines
Emerging Infectious Diseases
Phenotype
Organ Specificity
Zero Hunger
Female
Digestive Diseases
Spleen
Whole-Body Irradiation
Signal Transduction
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- The Journal of experimental medicine, vol 210, iss 10
- Accession number :
- edsair.dedup.wf.001..edd696b9c93cdd12c47871c5897f3e06