Active systemic lupus erythematosus is associated with failure of antigen-presenting cells to express programmed death ligand-1.
OBJECTIVE
Antigen-presenting cells (APC) play critical roles in establishing and maintaining peripheral tolerance. This is accomplished in part via expression of negative co-stimulatory molecules such as programmed death ligand-1 (PD-L1) on tolerogenic APC, such as immature myeloid dendritic cells (mDC). Several studies have strongly linked dysfunction of APC, including mDC, to the pathogenesis of SLE. The objective of this study was to determine whether APC expressed PD-L1 protein at normal levels during active lupus.


METHODS
Peripheral blood mononuclear cells (PBMC) were isolated from 19 paediatric patients with SLE and from 17 healthy age-matched controls. PBMC from both cohorts were cultured in the absence of exogenously added stimuli, and leucocyte PD-L1 expression was measured by flow cytometry.


RESULTS
Immature mDC and monocytes (Mo) from healthy children expressed little PD-L1 at initial isolation, but spontaneously up-regulated PD-L1 by 24 h. In contrast, both mDC and Mo from patients with active SLE failed to up-regulate PD-L1 over a 5 day time course, expressing this protein only during disease remissions.


CONCLUSIONS
These data are the first to link active lupus with reversibly decreased PD-L1 expression on professional APC, suggesting a novel mechanism for loss of peripheral tolerance in SLE.
Mozaffarian
N
N
Seattle Children's Hospital Research Institute, 1900 Ninth Avenue, 7th floor, Seattle, WA 98101, USA. neely.mozaffarian@seattlechildrens.org
Wiedeman
A E
AE
Stevens
A M
AM
D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism*; D060890:B7-H1 Antigen; D002478:Cells, Cultured; D002648:Child; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human