A crucial role for retinoic acid in the development of Notch-dependent murine splenic CD8−CD4−and CD4+dendritic cells
| Autor: | Georg Kraal, Reina E. Mebius, Marieke R. Beijer, Gera Goverse, Joke M. M. den Haan, Rosalie Molenaar |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Vitamin
medicine.medical_specialty RELB Immunology Retinoic acid chemical and pharmacologic phenomena Spleen Biology Acquired immune system medicine.disease Vitamin A deficiency chemistry.chemical_compound Endocrinology medicine.anatomical_structure Immune system chemistry Internal medicine medicine Immunology and Allergy CD8 |
| Zdroj: | European Journal of Immunology. 43:1608-1616 |
| ISSN: | 0014-2980 |
| DOI: | 10.1002/eji.201343325 |
| Popis: | The vitamin A metabolite retinoic acid is important for the function of the adaptive immune system, but the mechanism is not completely understood. Here we show that vitamin A is essential for the generation of Notch-dependent CD8(-) dendritic cells (DCs) in the spleen. We observed that CD8(-) CD4(-) (double negative (DN)) and CD4(+) DCs, but not CD8(+) DCs, express vitamin A regulated genes. To determine whether vitamin A levels influence splenic DC development, we generated mice that were fed a vitamin A-deficient diet. We detected a specific reduction of CD4(+) and DN DCs in the spleens of mice fed a vitamin A-deficient diet, while pre-DC numbers in both spleen and bone marrow were not affected. Vitamin A was specifically necessary for the development of RelB(high) , Notch-dependent CD4(+) , and DN DCs. In addition, DN DCs showed reduced proliferation during vitamin A deficiency. In contrast, mice that had received a diet with increased amounts of retinoic acid showed a significant expansion of Notch-dependent DN DCs. These data demonstrate that vitamin A stimulates the development of Notch-dependent splenic DCs and indicate that inefficient generation of DCs may contribute to the immune deficits observed during vitamin A deficiency. |
| Databáze: | OpenAIRE |
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