کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5667817 | 1592268 | 2017 | 16 صفحه PDF | دانلود رایگان |
- Mass cytometry analysis of pediatric SLE identifies a distinct monocyte signature characterized by MCP1, Mip1β and IL-1RA.
- The monocyte cytokine signature is induced by plasma circulating factors from clinical active SLE patients only.
- The monocyte cytokine signature is partially abrogated by IFNAR blockade and completely abrogated by selective JAK inhibition.
Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease with heightened disease severity in children. The incomplete understanding of the precise cellular and molecular events that drive disease activity pose a significant hurdle to the development of targeted therapeutic agents. Here, we performed single-cell phenotypic and functional characterization of pediatric SLE patients and healthy controls blood via mass cytometry. We identified a distinct CD14hi monocyte cytokine signature, with increased levels of monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein-1β (Mip1β), and interleukin-1 receptor antagonist (IL-1RA). This signature was shared by every clinically heterogeneous patient, and reproduced in healthy donors' blood upon ex-vivo exposure to plasma from clinically active patients only. This SLE-plasma induced signature was abrogated by JAK1/JAK2 selective inhibition. This study demonstrates the utility of mass cytometry to evaluate immune dysregulation in pediatric autoimmunity, by identification of a multi-parametric immune signature that can be further dissected to delineate the events that drive disease pathogenesis.
Journal: Journal of Autoimmunity - Volume 81, July 2017, Pages 74-89