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A novel innate lymphoid cell delineates childhood autoimmune arthritis [article]

Martin Del Castillo Velasco-Herrera, Matthew D Young, Felipe A Vieira Braga, Elizabeth C Rosser, Elena Miranda, Lucy Marshall, Meredyth G LI Wilkinson, Lira Mamanova, Mirjana Efremova, Roser Vento-Tormo, Alex Cagan, Ildiko Van Rhijn (+7 others)
2018 bioRxiv   pre-print

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Inflammation in autoimmune disease is mediated by a complex network of interacting cells. Their identity and cross-talk are encoded in messenger RNA (mRNA). Juvenile idiopathic arthritis (JIA), a chronic autoimmune arthritis of childhood, is characterised by synovial inflammation with infiltration of both innate and adaptive immune cells. Activated T cells play a role in disease but the cell types that drive the recruitment and activation of immune cells within the synovium are not known. Here,
more » ... we utilised droplet-based and full length single cell mRNA sequencing to obtain a quantitative map of the cellular landscape of JIA. We studied 45,715 cells from the synovial fluid of inflamed knee joints and peripheral blood. We identified a population of synovial innate lymphoid cells (ILCs), shared across patients, that exhibited a unique transcriptional profile in comparison to canonical ILC subtypes. Validation at protein-level across a spectrum of autoimmune arthritides revealed that these ILCs are pathologically expanded in a particular type of JIA. Using statistical tools to assess cellular interactions in synovial fluid, ILCs emerged as a central node of communication, expressing the full repertoire of genes required to orchestrate and maintain the inflammatory milieu. Several ILC-mediated signalling pathways may lend themselves as novel therapeutic targets. Together our findings demonstrate a distinct ILC subtype associated with a tissue-specific childhood autoimmune disease.
doi:10.1101/416784 fatcat:shbul3k4mrechekzb272luzd6a
Citation

Martin Del Castillo Velasco-Herrera, Matthew D Young, Felipe A Vieira Braga, Elizabeth C Rosser, Elena Miranda, Lucy Marshall, Meredyth G LI Wilkinson, Lira Mamanova, Mirjana Efremova, Roser Vento-Tormo, Alex Cagan, Ildiko Van Rhijn, David Branch Moody, Hussein Al-Mossawi, Sarah Teichmann, Adrienne M Flanagan, Lucy Wedderburn, Sam Behjati, Chrysothemis C Brown. "A novel innate lymphoid cell delineates childhood autoimmune arthritis." bioRxiv (2018)