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.
Volume
192
Issue
12
First Page
5586
Last Page
5598
ISSN
1550-6606
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.
Recommended Citation
Rodriguez-Pla A,
Patel P,
Maecker H,
Rossello-Urgell J,
Baldwin N,
Bennett L,
Cantrell V,
Baisch J,
Punaro M,
Gotte A,
Nassi L,
Wright T,
Palucka A,
Banchereau J,
Pascual V.
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes. J Immunol 2014 Jun 15; 192(12):5586-98.