PMID- 19915049 OWN - NLM STAT- MEDLINE DCOM- 20091222 LR - 20231006 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 183 IP - 11 DP - 2009 Dec 1 TI - Absence of the transcriptional repressor Blimp-1 in hematopoietic lineages reveals its role in dendritic cell homeostatic development and function. PG - 7039-46 LID - 10.4049/jimmunol.0901543 [doi] AB - Dendritic cells (DCs) are important for the initiation and regulation of immune responses. In this study, we demonstrate that DC homeostatic development in peripheral lymphoid organs is negatively regulated by the transcriptional repressor, Blimp-1, which is critical for regulation of plasma cell differentiation and T cell homeostasis and function. Deletion of Prdm1, the gene encoding Blimp-1, in mouse hematopoietic lineages resulted in an increase in the steady-state number of conventional DCs (cDCs). Specifically, Prdm1 deletion increased immediate CD8(-) cDC precursors in peripheral lymphoid organs, causing selective expansion of the CD8(-) cDC population. Upon stimulus-induced maturation, Blimp-1 was up-regulated in bone marrow-derived DCs via the p38 MAPK and NF-kappaB pathways. Notably, Blimp-1-deficient DCs matured poorly upon stimulation in vitro and in vivo. Blimp-1 binds to the proinflammatory cytokine/chemokine genes, Il-6 and Ccl2, and negatively regulates their expression. Collectively, our findings reveal two new roles for Blimp-1: negative regulation of a select subset of cDCs during homeostatic development, and enhancement of DC maturation. FAU - Chan, Yueh-Hsuan AU - Chan YH AD - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. FAU - Chiang, Ming-Feng AU - Chiang MF FAU - Tsai, Yueh-Chiao AU - Tsai YC FAU - Su, Shin-Tang AU - Su ST FAU - Chen, Ming-Hsu AU - Chen MH FAU - Hou, Mau-Sheng AU - Hou MS FAU - Lin, Kuo-I AU - Lin KI LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091113 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Prdm1 protein, mouse) RN - 0 (Transcription Factors) RN - EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1) SB - IM MH - Animals MH - Blotting, Western MH - Cell Differentiation/*immunology MH - Cell Lineage/*immunology MH - Chromatin Immunoprecipitation MH - Dendritic Cells/*cytology/immunology/metabolism MH - Electrophoretic Mobility Shift Assay MH - Flow Cytometry MH - Fluorescent Antibody Technique MH - Homeostasis/*immunology MH - Lymphocyte Culture Test, Mixed MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Positive Regulatory Domain I-Binding Factor 1 MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/genetics/immunology MH - Transcription Factors/genetics/*immunology/metabolism EDAT- 2009/11/17 06:00 MHDA- 2009/12/23 06:00 CRDT- 2009/11/17 06:00 PHST- 2009/11/17 06:00 [entrez] PHST- 2009/11/17 06:00 [pubmed] PHST- 2009/12/23 06:00 [medline] AID - jimmunol.0901543 [pii] AID - 10.4049/jimmunol.0901543 [doi] PST - ppublish SO - J Immunol. 2009 Dec 1;183(11):7039-46. doi: 10.4049/jimmunol.0901543. Epub 2009 Nov 13.