Title

IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.

Document Type

Article

Publication Date

6-15-2014

JAX Source

J Immunol 2014 Jun 15; 192(12):5586-98.

PMID

24829414

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. J Immunol 2014 Jun 15; 192(12):5586-98.