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Complement receptor CD46 co-stimulates optimal human CD8+ T cell effector function via fatty acid metabolism

Author

Listed:
  • Giuseppina Arbore

    (San Raffaele Scientific Institute
    King’s College London)

  • Erin E. West

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH))

  • Jubayer Rahman

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH))

  • Gaelle Friec

    (King’s College London)

  • Nathalie Niyonzima

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)
    Norwegian University of Science and Technology)

  • Mehdi Pirooznia

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH))

  • Ilker Tunc

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH))

  • Polychronis Pavlidis

    (King’s College London)

  • Nicholas Powell

    (King’s College London)

  • Yuesheng Li

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH))

  • Poching Liu

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH))

  • Aude Servais

    (Hôpital Necker)

  • Lionel Couzi

    (Dialyse, CHU Bordeaux, and CNRS-UMR 5164 Immuno ConcEpT, Université de Bordeaux)

  • Veronique Fremeaux-Bacchi

    (Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, and INSERM UMR S1138, Centre de Recherche des Cordeliers)

  • Leo Placais

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH))

  • Alastair Ferraro

    (Nottingham University Hospitals, NHS Trust)

  • Patrick R. Walsh

    (Institute of Cellular Medicine, Newcastle University)

  • David Kavanagh

    (Institute of Cellular Medicine, Newcastle University)

  • Behdad Afzali

    (National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)
    Immunoregulation Section, Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH)

  • Paul Lavender

    (King’s College London)

  • Helen J. Lachmann

    (University College London, Royal Free Campus)

  • Claudia Kemper

    (King’s College London
    National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)
    University of Lübeck)

Abstract

The induction of human CD4+ Th1 cells requires autocrine stimulation of the complement receptor CD46 in direct crosstalk with a CD4+ T cell-intrinsic NLRP3 inflammasome. However, it is unclear whether human cytotoxic CD8+ T cell (CTL) responses also rely on an intrinsic complement-inflammasome axis. Here we show, using CTLs from patients with CD46 deficiency or with constitutively-active NLRP3, that CD46 delivers co-stimulatory signals for optimal CTL activity by augmenting nutrient-influx and fatty acid synthesis. Surprisingly, although CTLs express NLRP3, a canonical NLRP3 inflammasome is not required for normal human CTL activity, as CTLs from patients with hyperactive NLRP3 activity function normally. These findings establish autocrine complement and CD46 activity as integral components of normal human CTL biology, and, since CD46 is only present in humans, emphasize the divergent roles of innate immune sensors between mice and men.

Suggested Citation

  • Giuseppina Arbore & Erin E. West & Jubayer Rahman & Gaelle Friec & Nathalie Niyonzima & Mehdi Pirooznia & Ilker Tunc & Polychronis Pavlidis & Nicholas Powell & Yuesheng Li & Poching Liu & Aude Servais, 2018. "Complement receptor CD46 co-stimulates optimal human CD8+ T cell effector function via fatty acid metabolism," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06706-z
    DOI: 10.1038/s41467-018-06706-z
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