PMID- 24227775 OWN - NLM STAT- MEDLINE DCOM- 20140218 LR - 20211021 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 191 IP - 12 DP - 2013 Dec 15 TI - Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8alpha+ dendritic cell development. PG - 5993-6001 LID - 10.4049/jimmunol.1203541 [doi] AB - Dendritic cells (DCs) are heterogeneous cell populations represented by different subtypes, each varying in terms of gene expression patterns and specific functions. Recent studies identified transcription factors essential for the development of different DC subtypes, yet molecular mechanisms for the developmental program and functions remain poorly understood. In this study, we developed and characterized a mouse DC progenitor-like cell line, designated DC9, from Irf8(-/-) bone marrow cells as a model for DC development and function. Expression of Irf8 in DC9 cells led to plasmacytoid DCs and CD8alpha(+) DC-like cells, with a concomitant increase in plasmacytoid DC- and CD8alpha(+) DC-specific gene transcripts and induction of type I IFNs and IL12p40 following TLR ligand stimulation. Irf8 expression in DC9 cells led to an increase in Id2 and Batf3 transcript levels, transcription factors shown to be important for the development of CD8alpha(+) DCs. We show that, without Irf8, expression of Id2 and Batf3 was not sufficient for directing classical CD8alpha(+) DC development. When coexpressed with Irf8, Batf3 and Id2 had a synergistic effect on classical CD8alpha(+) DC development. We demonstrate that Irf8 is upstream of Batf3 and Id2 in the classical CD8alpha(+) DC developmental program and define the hierarchical relationship of transcription factors important for classical CD8alpha(+) DC development. FAU - Jaiswal, Hemant AU - Jaiswal H AD - Laboratory of Innate Immunity, National Institute of Immunology, New Delhi 110067, India; FAU - Kaushik, Monika AU - Kaushik M FAU - Sougrat, Rachid AU - Sougrat R FAU - Gupta, Monica AU - Gupta M FAU - Dey, Anup AU - Dey A FAU - Verma, Rohit AU - Verma R FAU - Ozato, Keiko AU - Ozato K FAU - Tailor, Prafullakumar AU - Tailor P LA - eng GR - Z99 HD999999/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131113 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Basic-Leucine Zipper Transcription Factors) RN - 0 (CD8 Antigens) RN - 0 (CD8 antigen, alpha chain) RN - 0 (Idb2 protein, mouse) RN - 0 (Inhibitor of Differentiation Protein 2) RN - 0 (Interferon Regulatory Factors) RN - 0 (Interferon-alpha) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Repressor Proteins) RN - 0 (SNFT protein, mouse) RN - 0 (flt3 ligand protein) RN - 0 (interferon regulatory factor-8) SB - IM MH - Animals MH - Basic-Leucine Zipper Transcription Factors/biosynthesis/genetics/*physiology MH - CD8 Antigens/analysis MH - Cell Differentiation/drug effects MH - Cell Line MH - Dendrites/ultrastructure MH - Dendritic Cells/chemistry/classification/*cytology/ultrastructure MH - Gene Expression Regulation/*immunology MH - Hematopoietic Stem Cells/cytology MH - Inhibitor of Differentiation Protein 2/biosynthesis/genetics/*physiology MH - Interferon Regulatory Factors/biosynthesis/genetics/*physiology MH - Interferon-alpha/biosynthesis/genetics MH - Interleukin-12 Subunit p40/biosynthesis/genetics MH - Membrane Proteins/pharmacology MH - Mice MH - RNA, Messenger/biosynthesis/genetics MH - Recombinant Fusion Proteins/metabolism MH - Repressor Proteins/biosynthesis/genetics/*physiology MH - Transduction, Genetic PMC - PMC4805111 MID - NIHMS768648 EDAT- 2013/11/15 06:00 MHDA- 2014/02/19 06:00 PMCR- 2016/03/23 CRDT- 2013/11/15 06:00 PHST- 2013/11/15 06:00 [entrez] PHST- 2013/11/15 06:00 [pubmed] PHST- 2014/02/19 06:00 [medline] PHST- 2016/03/23 00:00 [pmc-release] AID - jimmunol.1203541 [pii] AID - 10.4049/jimmunol.1203541 [doi] PST - ppublish SO - J Immunol. 2013 Dec 15;191(12):5993-6001. doi: 10.4049/jimmunol.1203541. Epub 2013 Nov 13.