IFN 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 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.
Baylor Institute for Immunology Research, Dallas, TX 75204;
Alicia
A
Rodriguez-Pla
Baylor Institute for Immunology Research, Dallas, TX 75204;
Pinakeen
P
Patel
Human Immune Monitoring Center, Institute for Immunity, Transplantation, and Infection, Stanford University Medical Center, Stanford, CA 94305;
Holden T
HT
Maecker
Baylor Institute for Immunology Research, Dallas, TX 75204;
Jose
J
Rossello-Urgell
Baylor Institute for Immunology Research, Dallas, TX 75204;
Nicole
N
Baldwin
Baylor Institute for Immunology Research, Dallas, TX 75204;
Lynda
L
Bennett
Baylor Institute for Immunology Research, Dallas, TX 75204;
Victoria
V
Cantrell
Baylor Institute for Immunology Research, Dallas, TX 75204;
Jeanine
J
Baisch
Division of Pediatric Rheumatology, Texas Scottish Rite Hospital for Children, Dallas, TX 75219; and University of Texas Southwestern Medical Center, Dallas, TX 75235.
Marilynn
M
Punaro
Division of Pediatric Rheumatology, Texas Scottish Rite Hospital for Children, Dallas, TX 75219; and University of Texas Southwestern Medical Center, Dallas, TX 75235.
Alisa
A
Gotte
Division of Pediatric Rheumatology, Texas Scottish Rite Hospital for Children, Dallas, TX 75219; and University of Texas Southwestern Medical Center, Dallas, TX 75235.
Lorien
L
Nassi
Division of Pediatric Rheumatology, Texas Scottish Rite Hospital for Children, Dallas, TX 75219; and University of Texas Southwestern Medical Center, Dallas, TX 75235.
Tracey
T
Wright
Baylor Institute for Immunology Research, Dallas, TX 75204;
Anna Karolina
AK
Palucka
Baylor Institute for Immunology Research, Dallas, TX 75204;
Jacques
J
Banchereau
Baylor Institute for Immunology Research, Dallas, TX 75204; Division of Pediatric Rheumatology, Texas Scottish Rite Hospital for Children, Dallas, TX 75219; and VirginiP@Baylorhealth.edu.
Virginia
V
Pascual
D000293:Adolescent; D000328:Adult; D002465:Cell Movement / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D054400:Receptors, CCR7 / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology
C515370:CCR7 protein, human; D016207:Cytokines; D007370:Interferon Type I; D008070:Lipopolysaccharides; D054400:Receptors, CCR7; D051193:Toll-Like Receptors