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Id2 expression delineates differential checkpoints in the genetic program of CD8 alpha(+) and CD103(+) dendritic cell lineages


Jackson, JT; Hu, YF; Liu, RJ; Masson, F; D'Amico, A; Carotta, S; Xin, A; Camilleri, MJ; Mount, AM; Kallies, A; Wu, L; Smyth, GK; Nutt, SL; Belz, GT
2011-07-06
EMBO JOURNAL
Journal Article
30
13
2690-2704
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
NATURE PUBLISHING GROUP
IFN REGULATORY FACTOR-2; IN-VIVO; SUBSET DEVELOPMENT; CROSS-PRESENTATION; LANGERHANS CELLS; CUTTING EDGE; T-CELLS; GM-CSF; MOUSE; MICE
10.1038/emboj.2011.163
Refer to copyright notice on published article.