IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes Academic Article uri icon

Overview

MeSH Major

  • Cell Movement
  • Dendritic Cells
  • Interferon Type I
  • Lupus Erythematosus, Systemic

abstract

  • Blood monocytes from children with systemic lupus erythematosus (SLE) behave similar to dendritic cells (DCs), and SLE serum induces healthy monocytes to differentiate into DCs in a type I IFN-dependent manner. In this study, we found that these monocytes display significant transcriptional changes, including a prominent IFN signature, compared with healthy controls. Few of those changes, however, explain DC function. Exposure to allogeneic T cells in vitro reprograms SLE monocytes to acquire DC phenotype and function, and this correlates with both IFN-inducible (IP10) and proinflammatory cytokine (IL-1β and IL6) expression. Furthermore, we found that both IFN and SLE serum induce the upregulation of CCR7 transcription in these cells. CCR7 protein expression, however, requires a second signal provided by TLR agonists such as LPS. Thus, SLE serum "primes" a subset of monocytes to readily (<24 h) respond to TLR agonists and acquire migratory DC properties. Our findings might explain how microbial infections exacerbate lupus.

publication date

  • June 15, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5467885

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1301319

PubMed ID

  • 24829414

Additional Document Info

start page

  • 5586

end page

  • 98

volume

  • 192

number

  • 12