Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, UK; NIHR Biomedical Research Centre, Asthma UK Centre in Allergic Mechanisms of Asthma, London, Imperial College London, London, UK.
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.
固有免疫细胞在过敏原免疫治疗中发挥作用，使致敏过敏原产生免疫耐受的作用尚不清楚。在这里，我们报告了产生白细胞介素-10 的 2 型先天淋巴样细胞（IL-10 ILC2）在调节草花粉过敏中的作用。我们证明，KLRG1 但不是 KLRG1 ILC2 在受到 IL-33 和维甲酸激活后产生白细胞介素-10。这些细胞减弱了 Th 反应并维持了上皮细胞的完整性。与健康受试者相比，患有草花粉过敏的患者体内的 IL-10 KLRG1 ILC2 减少。在一项前瞻性、双盲、安慰剂对照试验中，我们证明了接受草花粉舌下免疫治疗的患者中 ILC2 产生白细胞介素-10 的能力得到了恢复。潜在的机制与 ILC 中视黄醇代谢途径、细胞因子-细胞因子受体相互作用和 JAK-STAT 信号通路的修饰有关。总之，我们的研究结果强调了 IL-10 ILC2 在过敏原免疫治疗的疾病修饰作用中的贡献。
