TY - JOUR
T1 - IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes
AU - Rodriguez-Pla, Alicia
AU - Patel, Pinakeen
AU - Maecker, Holden T.
AU - Rossello-Urgell, Jose
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
AU - Pascual, Virginia
PY - 2014/6/15
Y1 - 2014/6/15
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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U2 - 10.4049/jimmunol.1301319
DO - 10.4049/jimmunol.1301319
M3 - Article
C2 - 24829414
AN - SCOPUS:84902212735
SN - 0022-1767
VL - 192
SP - 5586
EP - 5598
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -