期刊
EMBO JOURNAL
卷 30, 期 13, 页码 2690-2704出版社
WILEY
DOI: 10.1038/emboj.2011.163
关键词
antigen presentation; cross-presentation; differentiaton; Id2; priming; transcription factors
资金
- National Health and Medical Research Council of Australia
- Australian Research Council
- Swiss National Science Foundation
- Sylvia and Charles Viertel Foundation
- Howard Hughes Medical Institute
- Pfizer Australia
Dendritic cells (DCs) have critical roles in the induction of the adaptive immune response. The transcription factors Id2, Batf3 and Irf-8 are required for many aspects of murine DC differentiation including development of CD8 alpha(+) and CD103(+) DCs. How they regulate DC subset specification is not completely understood. Using an Id2-GFP reporter system, we show that Id2 is broadly expressed in all cDC subsets with the highest expression in CD103(+) and CD8 alpha(+) lineages. Notably, CD103(+) DCs were the only DC able to constitutively cross-present cell-associated antigens in vitro. Irf-8 deficiency affected loss of development of virtually all conventional DCs (cDCs) while Batf3 deficiency resulted in the development of Sirp-alpha(-) DCs that had impaired survival. Exposure to GM-CSF during differentiation induced expression of CD103 in Id2-GFP(+) DCs. It did not restore cross-presenting capacity to Batf3(-/-) or CD103(-)Sirp-alpha-DCs in vitro. Thus, Irf-8 and Batf3 regulate distinct stages in DC differentiation during the development of cDCs. Genetic mapping DC subset differentiation using Id2-GFP may have broad implications in understanding the interplay of DC subsets during protective and pathological immune responses. The EMBO Journal (2011) 30, 2690-2704. doi:10.1038/emboj.2011.163; Published online 17 May 2011
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