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

Korneliusz Golebski, Janice A. Layhadi, Umit Sahiner, Esther H. Steveling-Klein, Madison M. Lenormand, Rachael C.Y. Li, Suzanne M. Bal, Balthasar A. Heesters, Gemma Vilà-Nadal, Oliver Hunewald, Guillem Montamat, Feng Q. He, Markus Ollert, Oleksandra Fedina, Mongkol Lao-Araya, Susanne J.H. Vijverberg, Anke Hilse Maitland-van der Zee, Cornelis M. van Drunen, Wytske J. Fokkens, Stephen R. DurhamHergen Spits*, Mohamed H. Shamji

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

109 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)291-307.e7
Issue number2
Publication statusPublished - 9 Feb 2021


  • IL-10
  • KLRG1
  • allergen specific immunotherapy
  • allergy
  • group 2 innate lymphoid cells
  • immunotherapy
  • innate lymphoid cells
  • plasticity
  • retinoic acid


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