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

Blood monocytes from children with systemic lupus erythematosus (SLE) behave like dendritic cells (DCs), and SLE serum induces healthy monocytes to differentiate into DCs in a type I Interferon (IFN)-dependent manner. Here, we found that these monocytes display significant transcriptional changes, i...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2014-05, Vol.192 (12), p.5586-5598
Main Authors: Rodriguez-Pla, Alicia, Patel, Pinakeen, Maecker, Holden T., Rossello-Urgell, Jose, Baldwin, Nicole, Bennett, Lynda, Cantrell, Victoria, Baisch, Jeanine, Punaro, Marilynn, Gotte, Alisa, Nassi, Lorien, Wright, Tracey, Palucka, Anna Karolina, Banchereau, Jacques, Pascual, Virginia
Format: Article
Language:English
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Summary:Blood monocytes from children with systemic lupus erythematosus (SLE) behave like dendritic cells (DCs), and SLE serum induces healthy monocytes to differentiate into DCs in a type I Interferon (IFN)-dependent manner. Here, we found that these monocytes display significant transcriptional changes, including a prominent IFN signature, compared to 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 pro-inflammatory cytokine ( IL1b and IL6 ) expression. Furthermore, we found that both IFN and SLE serum induce the upregulation of CCR7 transcription in these cells. CCR7 protein expression requires however a second signal provided by TLR agonists such as LPS. Thus, SLE serum “primes” a subset of monocytes to readily (
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1301319