Absence of the transcriptional repressor Blimp-1 in hematopoietic lineages reveals its role in dendritic cell homeostatic development and function.
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.
Chan
Yueh-Hsuan
YH
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Chiang
Ming-Feng
MF
Tsai
Yueh-Chiao
YC
Su
Shin-Tang
ST
Chen
Ming-Hsu
MH
Hou
Mau-Sheng
MS
Lin
Kuo-I
KI
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D047369:Chromatin Immunoprecipitation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006706:Homeostasis / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1