Eosinophils promote effector functions of lung group 2 innate lymphoid cells in allergic airway inflammation in mice.

Autor: LeSuer WE; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz., Kienzl M; Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria., Ochkur SI; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz., Schicho R; Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria., Doyle AD; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz., Wright BL; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz; Division of Pulmonology, Phoenix Children's Hospital, Phoenix, Ariz., Rank MA; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz; Division of Pulmonology, Phoenix Children's Hospital, Phoenix, Ariz., Krupnick AS; Department of Surgery, University of Maryland, Baltimore, Md., Kita H; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz; Department of Immunology, Mayo Clinic Arizona, Scottsdale, Ariz., Jacobsen EA; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Ariz; Department of Immunology, Mayo Clinic Arizona, Scottsdale, Ariz. Electronic address: jacobsen.elizabeth@mayo.edu.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2023 Aug; Vol. 152 (2), pp. 469-485.e10. Date of Electronic Publication: 2023 Apr 06.
DOI: 10.1016/j.jaci.2023.03.023
Abstrakt: Background: Group 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 respiratory inflammation, releasing IL-5 and IL-13 and promoting the pulmonary eosinophilia associated with allergen provocation. Although ILC2s have been shown to promote eosinophil activities, the role of eosinophils in group 2 innate lymphoid cell (ILC2) responses is less well defined.
Objective: We sought to investigate the role of eosinophils in activation of ILC2s in models of allergic asthma and in vitro.
Methods: Inducible eosinophil-deficient mice were exposed to allergic respiratory inflammation models of asthma, such as ovalbumin or house dust mite challenge, or to innate models of type 2 airway inflammation, such as inhalation of IL-33. Eosinophil-specific IL-4/13-deficient mice were used to address the specific roles for eosinophil-derived cytokines. Direct cell interactions between ILC2s and eosinophils were assessed by in vitro culture experiments.
Results: Targeted depletion of eosinophils resulted in significant reductions of total and IL-5 + and IL-13 + lung ILC2s in all models of respiratory inflammation. This correlated with reductions in IL-13 levels and mucus in the airway. Eosinophil-derived IL-4/13 was necessary for both eosinophil and ILC2 accumulation in lung in allergen models. In vitro, eosinophils released soluble mediators that induced ILC2 proliferation and G protein-coupled receptor-dependent chemotaxis of ILC2s. Coculture of ILC2s and IL-33-activated eosinophils resulted in transcriptome changes in both ILC2s and eosinophils, suggesting potential novel reciprocal interactions.
Conclusion: These studies demonstrate that eosinophils play a reciprocal role in ILC2 effector functions as part of both adaptive and innate type 2 pulmonary inflammatory events.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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