2. Academic Validation
  3. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells

CD1a presentation of endogenous antigens by group 2 innate lymphoid cells

  • Sci Immunol. 2017 Dec 22;2(18):eaan5918. doi: 10.1126/sciimmunol.aan5918.
Clare S Hardman 1,  Yi-Ling Chen 1,  Maryam Salimi 1,  Rachael Jarrett 1,  David Johnson 2,  Valtteri J Järvinen 3,  Raymond J Owens 3,  Emmanouela Repapi 4,  David J Cousins 5 6,  Jillian L Barlow 7,  Andrew N J McKenzie 7,  Graham Ogg 8
Affiliations

Affiliations

  • 1 Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, National Institute for Health Research (NIHR) Biomedical Research Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • 2 Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • 3 Oxford Protein Production Facility-UK, Harwell and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • 4 Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • 5 Department of Infection, Immunity and Inflammation, NIHR Leicester Respiratory Biomedical Research Unit, University of Leicester, Leicester, UK.
  • 6 MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
  • 7 MRC Laboratory of Molecular Biology, Cambridge, UK.
  • 8 Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, National Institute for Health Research (NIHR) Biomedical Research Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. graham.ogg@ndm.ox.ac.uk.
PMID: 29273672 DOI: 10.1126/sciimmunol.aan5918
Abstract

Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in Infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and Infection, activated by the presentation of endogenous neolipid antigens and Bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention.

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