Eosinophils promote effector functions of lung group 2 innate lymphoid cells in allergic airway inflammation in mice
Year: 2023
Type: article
Abstract: 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: 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.
Language: English
Topic: IL-33, ST2, and ILC Pathways
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
Funders: Mayo Clinic, American Lung Association, Mayo Foundation for Medical Education and Research, Austrian Science Fund, Medizinische Universität Graz, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1102402821, G1856673377, G205215200, Eosinophil Activities in Murine Models of Lung Disease, G3541206979, Imaging Functionally Distinct Eosinophil Subtypes Within Tissue Biopsies Using Gene Expression Profiling and an In Situ Hybridization Approach based on a Concurrent Multiple RNA Targeting Strategy, G4210535149, G645727997, Prostaglandin and cannabinoid receptors in EoE, Immune-endocannabinoid system and tumor microenvironment, G9000068547, The Role of Donor-Derived Eosinophils on Lung Allograft Ischemia Reperfusion Injury, Targeting a Defined Surgical Stress-Induced Inflammatory Pathway to Improve Peri-Operative Outcomes, Role of Eosinophils in Hepatic Ischemia Reperfusion Injury, G915378206
OpenAlex ID: W4362640377