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

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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

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Systemic Lupus Erythematosus
Dendritic Cells
Monocytes
Serum
Interleukin-1
Interleukin-6
Up-Regulation
Cytokines
T-Lymphocytes
Phenotype
Infection
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Rodriguez-Pla, A., Patel, P., Maecker, H. T., Rossello-Urgell, J., Baldwin, N., Bennett, L., ... 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

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

In: Journal of Immunology, Vol. 192, No. 12, 15.06.2014, p. 5586-5598.

Research output: Contribution to journalArticle

Rodriguez-Pla, A, Patel, P, Maecker, HT, Rossello-Urgell, J, Baldwin, N, Bennett, L, Cantrell, V, Baisch, J, Punaro, M, Gotte, A, Nassi, L, Wright, T, Palucka, AK, 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, vol. 192, no. 12, pp. 5586-5598. https://doi.org/10.4049/jimmunol.1301319
Rodriguez-Pla A, Patel P, Maecker HT, Rossello-Urgell J, Baldwin N, Bennett L et al. IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes. Journal of Immunology. 2014 Jun 15;192(12):5586-5598. https://doi.org/10.4049/jimmunol.1301319
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. / IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes. In: Journal of Immunology. 2014 ; Vol. 192, No. 12. pp. 5586-5598.
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AU - Baldwin, Nicole

AU - Bennett, Lynda

AU - Cantrell, Victoria

AU - Baisch, Jeanine

AU - Punaro, Marilynn

AU - Gotte, Alisa

AU - Nassi, Lorien

AU - Wright, Tracey

AU - Palucka, Anna Karolina

AU - Banchereau, Jacques

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N2 - 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.

AB - 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.

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