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Deep phenotyping detects a pathological CD4+ T-cell complosome signature in systemic sclerosis

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Fig. 1: T cells from patients with diffuse cutaneous scleroderma have reduced capacity for Th1 contraction and a distinct complosome signature.

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Acknowledgements

We thank the patients and the healthy donors for their support. This work was financed by MRC Centre grant MR/J006742/1, an EU-funded Innovative Medicines Initiative BTCURE (C.K.), a Wellcome Trust Investigator Award (C.K.), the King’s Bioscience Institute at King’s College London (G.A.), The King’ College London BRC Genomics Facility, the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, National Institute Of Health grant R21 AI123789 (D.E.H.) and by the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH (C.K.). D.E.H. and L.M. are grateful for the support of the Washington University School of Medicine Immunomonitoring Laboratory. V.H.O., C.P.D. and D.A. are grateful for funding support from Versus Arthritis, Scleroderma & Raynaud’s UK, Rosetrees Trust and Royal Free Charity. T.M.W. is supported by a National Health and Medical Research Council Fellowship (1105420). SK is supported by Cancer Research UK (CRUK).  The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Center awarded to Guy’s & St Thomas’ NHS Foundation Trust in Partnership with King’s College London and King’s College Hospital NHS Foundation Trust.

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D.E.H, C.K. and S.K. conceived and directed the study, performed experiments and wrote the manuscript. G.A., B.C., L.P., T.M.W. and C.K. designed, performed and/or analyzed the T-cell activation and ‘rescue’ experiments. L.M., R.E., S.H., S.K., K.B. and P.N., generated and validated the heavy metal-conjugated CyTOF® compatible antibody panel and/or performed and/or analyzed the CyTOF experiments. V.H.O., D.A., and C.P.D. designed and analyzed the experiments and data derived from cells isolated from the patients. All authors discussed and edited the manuscript. G.A. and V.H.O. contributed equally to the work and are shared first authors.

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Correspondence to Shahram Kordasti or Claudia Kemper or Dennis E. Hourcade.

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Competing interests

T.M.W. is a co-inventor on a patent for C5aR2 agonists as immunomodulators for inflammatory disease. The authors have no additional financial interests.

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Arbore, G., Ong, V.H., Costantini, B. et al. Deep phenotyping detects a pathological CD4+ T-cell complosome signature in systemic sclerosis. Cell Mol Immunol 17, 1010–1013 (2020). https://doi.org/10.1038/s41423-019-0360-8

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