期刊
IMMUNITY
卷 54, 期 2, 页码 291-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2020.12.013
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资金
- Imperial College Trust
- NIHR Imperial Biomedical Research Centre
- ERC [341038]
- Luxembourg National Research Fund (FNR) [AFR-RIKEN/11228353/TregBAR, PRIDE/10907093/CRITICS, PRIDE/11012546/NEXTIMMUNE]
- European Research Council (ERC) [341038] Funding Source: European Research Council (ERC)
IL-10(+) ILC2s play a crucial role in modulating grass-pollen allergy, attenuating Th responses, and maintaining epithelial cell integrity. Patients with grass-pollen allergy have lower levels of IL-10(+) KLRG1(+) ILC2s, but this ability to produce IL-10 is restored after immunotherapy treatment. The mechanisms underlying this involve modifications in retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs.
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.
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