A novel innate lymphoid cell delineates childhood autoimmune arthritis

Velasco-Herrera, M. D. C.; Young, M. D.; Braga, F. A. V.; Rosser, E. C.; Miranda, E.; Marshall, L.; Wilkinson, M. G. L.; Mamanova, L.; Efremova, M.; Vento-Tormo, R.; Cagan, A.; Rhijn, I. V.; Moody, D. B.; Al-Mossawi, H.; Teichmann, S.; Flanagan, A. M.; Wedderburn, L.; Behjati, S.; Brown, C. C.

doi:10.1101/416784

bioRxiv · 10.1101/416784

A novel innate lymphoid cell delineates childhood autoimmune arthritis

Velasco-Herrera, M. D. C.·Young, M. D.·Braga, F. A. V.·Rosser, E. C.·Miranda, E.·Marshall, L.·Wilkinson, M. G. L.·Mamanova, L.·Efremova, M.·Vento-Tormo, R.·Cagan, A.·Rhijn, I. V.·Moody, D. B.·Al-Mossawi, H.·Teichmann, S.·Flanagan, A. M.·Wedderburn, L.·Behjati, S.·Brown, C. C.

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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.

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Velasco-Herrera, M. D. C., Young, M. D., Braga, F. A. V., Rosser, E. C., Miranda, E., Marshall, L., Wilkinson, M. G. L., Mamanova, L., Efremova, M., Vento-Tormo, R., Cagan, A., Rhijn, I. V., Moody, D. B., Al-Mossawi, H., Teichmann, S., Flanagan, A. M., Wedderburn, L., Behjati, S., Brown, C. C.. 2018-09-13. A novel innate lymphoid cell delineates childhood autoimmune arthritis. https://doi.org/10.1101/416784

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