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THU0022 Single Cell Interferon Signatures in Lupus Patient Monocytes Reveal a Differential Impact of Interferon Signaling Between Monocyte Subtypes
  1. Z. Jin,
  2. W. Fan,
  3. M.A. Jensen,
  4. J.M. Dorschner,
  5. D.M. Vsetecka,
  6. S. Amin,
  7. A. Makol,
  8. F. Ernste,
  9. T. Osborn,
  10. K. Moder,
  11. V. Chowdhary,
  12. T.B. Niewold
  1. Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, United States

Abstract

Background Type I interferon (IFN) is a primary pathogenic factor in human systemic lupus erythematosus (SLE). IFN signatures have been observed in immune cell populations.

Objectives We examined gene expression in individual monocytes from SLE patients in this study.

Methods CD14++CD16- classical monocytes (CLs) and CD14dimCD16+ non classical monocytes (NCLs) from SLE patients were purified by magnetic separation. The Fluidigm C1 System was used for single cell capture and target gene pre-amplification. Rt-PCR was used to quantify expression of 87 monocyte-related genes. An individual cell IFN score was generated based upon the expression of 17 IFN-induced genes.

Results Monocytes from the same SLE patient blood sample demonstrated varying levels of IFN-induced gene expression. In CLs, high IFN score correlated with CD32a, IL1B, and IL8 expression. In NCLs, high IFN score was correlated with 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, and MyD88. CD16 transcripts were detected in a small group of classical monocytes, despite a lack of surface CD16 expression. In these cells, CD16 expression was positively correlated with IFN score (p=0.019).

Conclusions This study reveals diverse IFN responses of individual monocytes, supports the idea that IFN signaling has distinct effects upon classical and non-classical monocytes. 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 which may be masked in whole blood or mixed cell populations.

Disclosure of Interest None declared

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