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

AI Article Synopsis

  • Dendritic cells (DCs) play a key role in immune responses, and this study shows that their development in lymphoid organs is negatively regulated by the protein Blimp-1.
  • Deleting the Prdm1 gene, which encodes Blimp-1, in mice led to an increase in a specific type of DCs (conventional DCs) and their precursors, particularly affecting the CD8(-) cDC population.
  • Blimp-1 not only promotes the maturation of DCs upon stimulus but also represses the expression of inflammatory genes like Il-6 and Ccl2, highlighting its dual function in DC development and maturation.

Article Abstract

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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Source
http://dx.doi.org/10.4049/jimmunol.0901543DOI Listing

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