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

Immunity. 2021 Feb 9;54(2):291-307.e7. doi: 10.1016/j.immuni.2020.12.013. Epub 2021 Jan 14.


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.

Keywords: IL-10; KLRG1; allergen specific immunotherapy; allergy; group 2 innate lymphoid cells; immunotherapy; innate lymphoid cells; plasticity; retinoic acid.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology
  • Double-Blind Method
  • Female
  • Humans
  • Immune Tolerance
  • Immunity, Innate
  • Interleukin-10 / metabolism*
  • Janus Kinases / metabolism
  • Lectins, C-Type / metabolism
  • Lymphocytes / immunology*
  • Male
  • Middle Aged
  • Placebo Effect
  • Poaceae / immunology
  • Pollen / immunology
  • Receptors, Immunologic / metabolism
  • Rhinitis, Allergic, Seasonal / immunology*
  • Rhinitis, Allergic, Seasonal / therapy
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Sublingual Immunotherapy / methods*
  • Th2 Cells / immunology
  • Treatment Outcome
  • Vitamin A / metabolism
  • Young Adult


  • Allergens
  • KLRG1 protein, human
  • Lectins, C-Type
  • Receptors, Immunologic
  • STAT Transcription Factors
  • Vitamin A
  • Interleukin-10
  • Janus Kinases