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

February 09, 2021 By:
  • Golebski K
  • Layhadi JA
  • Sahiner U
  • Steveling-Klein EH
  • Lenormand MM
  • Li RCY
  • Bal SM
  • Heesters BA
  • Vila-Nadal G
  • Hunewald O
  • Montamat G
  • He FQ
  • Ollert M
  • Fedina O
  • Lao-Araya M
  • Vijverberg SJH
  • Maitland-van der Zee AH
  • van Drunen CM
  • Fokkens WJ
  • Durham SR
  • Spits H
  • Shamji MH.

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.

2021 Feb. Immunity.54(2):291-307 e7. Epub 2021 Jan 14.
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