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

Alicia Rodriguez-Pla, Pinakeen Patel, Holden T. Maecker, Jose Rossello-Urgell, Nicole Baldwin, Lynda Bennett, Victoria Cantrell, Jeanine Baisch, Marilynn Punaro, Alisa Gotte, Lorien Nassi, Tracey Wright, Anna Karolina Palucka, Jacques Banchereau, Virginia Pascual

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5586-5598
Number of pages13
JournalJournal of Immunology
Volume192
Issue number12
DOIs
StatePublished - Jun 15 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rodriguez-Pla, A., Patel, P., Maecker, H. T., Rossello-Urgell, J., Baldwin, N., Bennett, L., Cantrell, V., Baisch, J., Punaro, M., Gotte, A., Nassi, L., Wright, T., Palucka, A. K., Banchereau, J., & Pascual, V. (2014). IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes. Journal of Immunology, 192(12), 5586-5598. https://doi.org/10.4049/jimmunol.1301319