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

journal contribution
posted on 05.01.2018, 14:09 by Clare S. Hardman, Yi-Ling Chen, Maryam Salimi, Rachael Jarrett, David Johnson, Valtteri J. Järvinen, Raymond J. Owens, Emmanouela Repapi, David J. Cousins, Jillian L. Barlow, Andrew N. J. McKenzie, Graham Ogg
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.

Funding

We were supported by NIHR Clinical Research Network, British Association of Dermatologists, British Skin Foundation, Misses Barrie Charitable Trust, Medical Research Council (CF7720, U105178805, MR/K018779/1), Wellcome Trust (090532/Z/09/Z), NIHR (NIHR) Oxford and Leicester Biomedical Research Centres (BRC).

History

Citation

Science Immunology, 2017, 2 (18) eaan5918

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

AM (Accepted Manuscript)

Published in

Science Immunology

Publisher

American Association for the Advancement of Science

eissn

2470-9468

Acceptance date

10/11/2017

Copyright date

2017

Available date

05/01/2018

Publisher version

http://immunology.sciencemag.org/content/2/18/eaan5918

Language

en

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