Session Type: Abstract Submissions (ACR)
Background/Purpose Type I interferon (IFN) is a primary pathogenic factor in human systemic lupus erythematosus (SLE). IFN gene expression signatures have been observed in whole blood and mixed peripheral blood mononuclear cell populations in SLE, but the significance of this IFN signaling in immune cell subsets is still incompletely understood. We examined gene expression in individual SLE patient monocytes to explore the impact of increased IFN-induced transcription in single cells.
Methods CD14++CD16- classical monocytes and CD14dimCD16+ non classical monocytes from SLE patients were purified by magnetic separation. The Fluidigm C1 System was used for single cell capture and target gene pre-amplification, and equal numbers of classical and non-classical monocytes were studied. rtPCR was used to quantify expression of 87 monocyte-related genes, 17 of which were IFN-induced genes. An individual cell IFN score was generated based upon the expression of the 17 IFN-induced genes.
Results Monocytes from the same SLE patient blood sample demonstrated varying levels of IFN-induced gene expression. In classical monocytes, high IFN score correlated with CD32a, IL1B, and IL8 expression. In non-classical monocytes, high IFN score was correlated with a larger number of inflammatory mediators, including cytokines such as IL12, IL23, and IL15; the immune receptors CD36, CD32a, CD80, and TLR7; and inflammatory signaling genes such as RELA, STAT2, IRAK1, IRAK4, and MyD88. CD16 transcripts were detected in a small group of classical monocytes, despite a lack of surface CD16 expression, suggesting that these cells may be transitioning from classical to non-classical subgroup. In these cells, CD16 expression was positively correlated with IFN score (p=0.019).
Conclusion This study revealed striking diversity in the IFN responses of individual monocytes, and supports the idea that IFN signaling has distinct effects upon classical and non-classical monocytes, as the IFN signature correlated with a diverse panel of inflammatory mediators in the non-classical subset. IFN may contribute to the transition from classical to non-classical subtype in SLE. Single cell studies can reveal effects of IFN on single immune cells and uncommon populations such as non-classical monocytes, which may be masked in whole blood or mixed cell populations.
M. A. Jensen,
J. M. Dorschner,
F. C. Ernste,
K. G. Moder,
T. B. Niewold,
Janssen Pharmaceutica Product, L.P., EMD Serono,
Biogen Idec, EMD Serono,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-cell-interferon-signatures-in-lupus-patient-monocytes-reveal-a-differential-impact-of-interferon-signaling-between-monocyte-subtypes/