Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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


  1. 1.

    Liszewski, M. K. et al. Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. Immunity 39, 1143–1157 (2013).

    CAS  Article  Google Scholar 

  2. 2.

    Arbore, G. et al. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4(+) T cells. Science 352, aad1210 (2016).

    Article  Google Scholar 

  3. 3.

    Kolev, M. et al. Complement regulates nutrient influx and metabolic reprogramming during Th1 cell responses. Immunity 42, 1033–1047 (2015).

    CAS  Article  Google Scholar 

  4. 4.

    West, E. E., Kolev, M. & Kemper, C. Complement and the regulation of T cell responses. Annu. Rev. Immunol. 36, 309–338 (2018).

    CAS  Article  Google Scholar 

  5. 5.

    Ellinghaus, U. et al. Dysregulated CD46 shedding interferes with Th1-contraction in systemic lupus erythematosus. Eur. J. Immunol. 47, 1200–1210 (2017).

  6. 6.

    Denton, C. P. & Khanna, D. Systemic sclerosis. Lancet 390, 1685–1699 (2017).

    Article  Google Scholar 

  7. 7.

    Kurasawa, K. et al. Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum. 43, 2455–2463 (2000).

    CAS  Article  Google Scholar 

  8. 8.

    Radstake, T. R. et al. The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypes. PLoS ONE 4, e5903 (2009).

    Article  Google Scholar 

  9. 9.

    Kordasti, S. et al. Deep phenotyping of Tregs identifies an immune signature for idiopathic aplastic anemia and predicts response to treatment. Blood 128, 1193–1205 (2016).

    CAS  Article  Google Scholar 

  10. 10.

    Povoleri, G. A. M. et al. Human retinoic acid-regulated CD161(+) regulatory T cells support wound repair in intestinal mucosa. Nat. Immunol. 19, 1403–1414 (2018).

    CAS  Article  Google Scholar 

Download references


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.

Author information




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.

Corresponding authors

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

Ethics declarations

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.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

Further reading


Quick links