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Publication : Absence of the transcriptional repressor Blimp-1 in hematopoietic lineages reveals its role in dendritic cell homeostatic development and function.

First Author  Chan YH Year  2009
Journal  J Immunol Volume  183
Issue  11 Pages  7039-46
PubMed ID  19915049 Mgi Jnum  J:157392
Mgi Id  MGI:4430767 Doi  10.4049/jimmunol.0901543
Citation  Chan YH, et al. (2009) Absence of the transcriptional repressor Blimp-1 in hematopoietic lineages reveals its role in dendritic cell homeostatic development and function. J Immunol 183(11):7039-46
abstractText  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.
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