Back to Search Results

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

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. Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, UK. Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London, London, UK; Department of Dermatology, Allergy Unit, University Hospital Basel, Basel, Switzerland. Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg. Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg; Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg; Department of Dermatology and Allergy Center, Odense Research Centre for Anaphylaxis (ORCA), University of Southern Denmark, Odense, Denmark. Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Department of Otorhinolaryngology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: hergen.spits@amsterdamumc.nl. 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. Electronic address: m.shamji@imperial.ac.uk.

Immunity. 2021;(2):291-307.e7
Full text from:

Other resources

Abstract

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.

Methodological quality

Publication Type : Randomized Controlled Trial

Metadata