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LeSuer, WE; Kienzl, M; Ochkur, SI; Schicho, R; Doyle, AD; Wright, BL; Rank, MA; Krupnick, AS; Kita, H; Jacobsen, EA.
Eosinophils promote effector functions of lung group 2 innate lymphoid cells in allergic airway inflammation in mice.
J Allergy Clin Immunol. 2023; 152(2):469-485.e10
Doi: 10.1016/j.jaci.2023.03.023
[OPEN ACCESS]
Web of Science
PubMed
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- Co-authors Med Uni Graz
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Kienzl Melanie
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Schicho Rudolf
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- 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: 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.
- Find related publications in this database (using NLM MeSH Indexing)
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Mice - administration & dosage
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Animals - administration & dosage
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Immunity, Innate - administration & dosage
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Eosinophils - metabolism
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Interleukin-33 - metabolism
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Interleukin-13 - metabolism
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Interleukin-5 - metabolism
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Interleukin-4 - metabolism
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Lymphocytes - administration & dosage
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Lung - administration & dosage
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Cytokines - metabolism
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Asthma - metabolism
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Inflammation - metabolism
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Allergens - metabolism
- Find related publications in this database (Keywords)
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Eosinophil
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group 2 innate lymphoid cell
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asthma
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IL-33
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IL-4
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IL-13
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lung
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inflammation
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eosinophil deficient