Research ArticleHUMAN IMMUNOLOGY

CD1a presentation of endogenous antigens by group 2 innate lymphoid cells

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Science Immunology  22 Dec 2017:
Vol. 2, Issue 18, eaan5918
DOI: 10.1126/sciimmunol.aan5918

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A new look at lipid surveillance

Human group 2 innate lymphoid cells (ILC2) play roles in maintaining homeostasis and defending against pathogens, but dysregulated ILC2 responses have been linked to asthma and allergic responses. Hardman et al. now use an in vivo human skin challenge model to show that ILC2 express CD1a, which is regulated by TSLP, and that CD1a+ILC2 can present endogenous lipid antigens to CD1a-reactive T cells and induce inflammatory responses. CD1a+ILC2 expressed the phospholipase PLA2G4A, which contributed to CD1a-mediated T cell activation, and this pathway was involved in sensing Staphylococcus aureus–associated skin inflammation. These results provide insight into lipid sensing by skin-resident ILC2 and how this pathway may contribute to atopic skin inflammation and pathogen surveillance.

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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