IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
J Immunol, 2014/6/15;192(12):5586-98.
Rodriguez-Pla A[1], Patel P[1], Maecker HT[2], Rossello-Urgell J[1], Baldwin N[1], Bennett L[1], Cantrell V[1], Baisch J[1], Punaro M[3], Gotte A[3], Nassi L[3], Wright T[3], Palucka AK[1], Banchereau J[1], Pascual V[4]
Affiliations
PMID: 24829414DOI: 10.4049/jimmunol.1301319
Impact factor: 5.426
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.
MeSH terms
Adolescent; Adult; Cell Movement; Child; Cytokines; Dendritic Cells; Female; Humans; Interferon Type I; Lipopolysaccharides; Lupus Erythematosus, Systemic; Receptors, CCR7; Toll-Like Receptors
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