| Summary: | Group 2 innate lymphoid cells (ILC2) are potent effectors of barrier immunity, with critical roles in infection, wound healing and allergy. In addition to rapid production of cytokines, a proportion of ILC2 express MHC-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 cell wall components. Here 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 on ILC2 is upregulated by TSLP 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 TLR-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a new 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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