Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response

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Golebski K., Layhadi J. A., Sahiner Ü. M., Steveling-Klein E. H., Lenormand M. M., Li R. C. Y., ...More

IMMUNITY, vol.54, no.2, pp.291-314, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 54 Issue: 2
  • Publication Date: 2021
  • Doi Number: 10.1016/j.immuni.2020.12.013
  • Journal Name: IMMUNITY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database, DIALNET
  • Page Numbers: pp.291-314
  • Hacettepe University Affiliated: Yes


The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10(+) ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1(+) but not KLRG1(-) ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10(+) KLRG1(+) ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10(+) ILC2s in the disease-modifying effect by allergen immunotherapy.