Immunotherapy for Upper Airway Disease Generates IL-10-Producing KLRG1 + ILC2s that are Associated with Clinical Benefit

SummaryIn this study, we addressed the role of IL-10-producing ILCs in controlling grass pollen allergy. IL-10+ ILCs are comprised in KLRG1+ILC2-lineage cells and absent on CRTH2+ ILC2 which lack KLRG1.  We observed that ILC2s in healthy subjects and grass pollen allergic patients show differential gene expression profiles. A cross-sectional study demonstrates that IL-10-producing KLRG1+ ILC2s are strongly reduced in patients with grass pollen and house dust mite allergy when compared to healthy subjects and those who have received grass pollen subcutaneous immunotherapy treatment. In a prospective double-blind, placebo-controlled trial of grass pollen sublingual immunotherapy (SLIT), we observed that the capacity of ILC2 to produce IL-10 was restored in patients who received SLIT, but not patients receiving a placebo. Finally, we demonstrated that these IL-10-producing ILCs are functional and play a crucial role in restoring barrier function and tissue balance in allergic diseases.