Id2 expression delineates differential checkpoints in the genetic program of CD8 alpha(+) and CD103(+) dendritic cell lineages
Details
Publication Year 2011-07-06, Volume 30, Issue #13, Page 2690-2704
Journal Title
EMBO JOURNAL
Publication Type
Journal Article
Abstract
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
Publisher
NATURE PUBLISHING GROUP
Keywords
IFN REGULATORY FACTOR-2; IN-VIVO; SUBSET DEVELOPMENT; CROSS-PRESENTATION; LANGERHANS CELLS; CUTTING EDGE; T-CELLS; GM-CSF; MOUSE; MICE
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Creation Date: 2011-07-06 12:00:00
Last Modified: 0001-01-01 12:00:00
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