P030 Transcriptional landscapes of memory T cells from patients with juvenile idiopathic arthritis
Authors: P Maschmeyer, GA Heinz, F Heinrich, P Durek, LE Wirth, SL von Stuckrad, K Lehmann, CL Tran, B Orak, H-D Chang, T Kallinich, A Radbruch, M-F Mashreghi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease (CID) of unknown origin and is characterized by joint inflammation in children and young adults.<sup>1</sup> 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.<sup>2 3</sup> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusions</h3> 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. <h3>References</h3> Prakken B, <i>et al</i>. Juvenile idiopathic arthritis. <i>Lancet</i> 2011. Niesner U, <i>et al</i>. Autoregulation of Th1-mediated inflammation by twist1. <i>J Exp Med</i> 2008. Maschmeyer P, <i>et al</i>. Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo. <i>J Autoimmun</i> 2018. <h3>Acknowledgements</h3> This work is supported by the European Regional Development Fund (ERDF 2014–2020 and EFRE 1.8/11). <h3>Disclosure of Interest</h3> None declared.