PMID- 21587207 OWN - NLM STAT- MEDLINE DCOM- 20110916 LR - 20211020 IS - 1460-2075 (Electronic) IS - 0261-4189 (Print) IS - 0261-4189 (Linking) VI - 30 IP - 13 DP - 2011 May 17 TI - Id2 expression delineates differential checkpoints in the genetic program of CD8alpha+ and CD103+ dendritic cell lineages. PG - 2690-704 LID - 10.1038/emboj.2011.163 [doi] AB - 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 CD8alpha(+) 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 CD8alpha(+) 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. FAU - Jackson, Jacob T AU - Jackson JT AD - Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. FAU - Hu, Yifang AU - Hu Y FAU - Liu, Ruijie AU - Liu R FAU - Masson, Frederick AU - Masson F FAU - D'Amico, Angela AU - D'Amico A FAU - Carotta, Sebastian AU - Carotta S FAU - Xin, Annie AU - Xin A FAU - Camilleri, Mary J AU - Camilleri MJ FAU - Mount, Adele M AU - Mount AM FAU - Kallies, Axel AU - Kallies A FAU - Wu, Li AU - Wu L FAU - Smyth, Gordon K AU - Smyth GK FAU - Nutt, Stephen L AU - Nutt SL FAU - Belz, Gabrielle T AU - Belz GT LA - eng GR - Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110517 PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Antigens, CD) RN - 0 (CD8 Antigens) RN - 0 (CD8 antigen, alpha chain) RN - 0 (Idb2 protein, mouse) RN - 0 (Inhibitor of Differentiation Protein 2) RN - 0 (Integrin alpha Chains) RN - 0 (alpha E integrins) SB - IM MH - Animals MH - Antigens, CD/*metabolism MH - CD8 Antigens/*metabolism MH - Cell Differentiation/genetics/physiology MH - Cell Lineage/*genetics MH - Cells, Cultured MH - Dendritic Cells/metabolism/*physiology MH - Gene Expression/physiology MH - Genes, cdc/physiology MH - Inhibitor of Differentiation Protein 2/*genetics/physiology MH - Integrin alpha Chains/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Models, Biological PMC - PMC3155298 COIS- The authors declare that they have no conflict of interest. EDAT- 2011/05/19 06:00 MHDA- 2011/09/17 06:00 PMCR- 2011/05/17 CRDT- 2011/05/19 06:00 PHST- 2011/02/24 00:00 [received] PHST- 2011/04/28 00:00 [accepted] PHST- 2011/05/19 06:00 [entrez] PHST- 2011/05/19 06:00 [pubmed] PHST- 2011/09/17 06:00 [medline] PHST- 2011/05/17 00:00 [pmc-release] AID - emboj2011163 [pii] AID - 10.1038/emboj.2011.163 [doi] PST - epublish SO - EMBO J. 2011 May 17;30(13):2690-704. doi: 10.1038/emboj.2011.163.