Author:
Velasco-Herrera Martin Del Castillo,Young Matthew D,Braga Felipe A Vieira,Rosser Elizabeth C.,Miranda Elena,Marshall Lucy,Wilkinson Meredyth G LI,Mamanova Lira,Efremova Mirjana,Vento-Tormo Roser,Cagen Alex,Al-Mossawi Hussein,Teichmann Sarah,Flanagan Adrienne M,Wedderburn Lucy,Behjati Sam,Brown Chrysothemis C.
Abstract
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 cells1. Activated T cells play a role in disease2 but the cell types that drive the recruitment and activation of immune cells within the synovium are not known. Here, 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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