P030 Transcriptional landscapes of memory T cells from patients with juvenile idiopathic arthritis. (March 2019)

• Record Type: Journal Article
• Authors: Maschmeyer, P; Heinz, GA; Heinrich, F; Durek, P; Wirth, LE; von Stuckrad, SL; Lehmann, K; Tran, CL; Orak, B; Chang, H-D; Kallinich, T; Radbruch, A; Mashreghi, M-F
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 1
• Page Start: A11
• Page End: A11
• Publication Date: 2019-03
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-EWRR2019.22
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Career situation of first and presenting author: Post-doctoral fellow. Introduction: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease (CID) of unknown origin and is characterized by joint inflammation in children and young adults. 1 Evidence suggests a strong contribution of memory T cells to disease pathogenicity in JIA. While few markers for T cells adapted to chronic inflammation have been identified. 2 3 a comprehensive analysis of what distinguishes pathogenic memory T cells in inflamed tissues of chronic inflammation from protective, circulating memory T cells is still lacking. Objectives: To characterize the transcriptional profiles of memory T cells that putatively maintain chronic inflammation in JIA patients. To identify biomarkers that are associated with autoantigen-specific clonotypes among memory T cells in JIA. Methods: Memory T cells were isolated from the synovial fluid (SF) and the peripheral blood (PB) of oligoarticular JIA patients and purified by fluorescence-activated cell sorting (FACS). Subsequently, single cell sequencing including T cell receptor (TCR) sequencing was performed on ∼18.000 memory T cells of each JIA patient. Results: Memory T cell populations both from the blood and from the SF are heterogenous populations according to their transcriptional expression patterns. The SF harbored a larger population of enriched T memory cell clonotypes than the blood. In addition, enriched memory T helper cell clones in the SF showed a transcriptional pattern of activation compared to non-enriched clonotypes. Finally, small subpopulations of enriched memory T helper cell clones in the SF show a transcriptional signature that resembles transcriptomes obtained by bulk sequencing. Thus, a rather small subpopulation of antigen-specific cells might be responsible for the overall transcriptional character of T cells found at the inflamed sites of CIDs. Conclusions: Single cell sequencing combined with TCR sequencing is a powerful tool to identify and characterize subsets of T memory cells in chronic inflammation. The obtained data might be useful to better understand how T cell subsets contribute to disease pathogenicity in CIDs and reveals putative targets that could be therapeutically exploited in order to selectively deplete pathogenic memory T cells. References: Prakken B, et al . Juvenile idiopathic arthritis. Lancet 2011. Niesner U, et al . Autoregulation of Th1-mediated inflammation by twist1. J Exp Med 2008. Maschmeyer P, et al . Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo. J Autoimmun 2018. Acknowledgements: This work is supported by the European Regional Development Fund (ERDF 2014–2020 and EFRE 1.8/11). Disclosure of Interest: None declared.