Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 134, Issue 3, Pages 671-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2014.06.024
Keywords
IL-33; IL-25; IL-5; IL-13; ILC2; innate immunity; asthma; allergy
Categories
Funding
- National Institutes of Health [AI34486, HL117823]
- Mayo Foundation
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Background: In mice, group 2 innate lymphoid cells (ILC2s) likely mediate helminth immunity, inflammation, and tissue repair and remodeling. However, the involvement of ILC2s in human diseases, such as asthma, is not well understood. Objectives: The goals of this study were to investigate whether peripheral blood specimens can be used to monitor innate type 2 immunity in human subjects and to examine whether ILC2s are involved in human asthma. Methods: PBMCs from subjects with allergic asthma (AA), subjects with allergic rhinitis (AR), or healthy control (HC) subjects were cultured in vitro with IL-25 or IL-33. Flow cytometry and cell sorting were used to identify, isolate, and quantitate ILC2s in PBMCs. Results: Human PBMCs produced IL-5 and IL-13 when stimulated with IL-33 or IL-25 in the presence of IL-2 without antigens. In addition, IL-7 or thymic stromal lymphopoietin were able to replace IL-2. The cell population with phenotypic ILC2 characteristics, lineage(-) CD127(+) CRTH2(+) cells, responded to IL-33 and produced large quantities of IL-5 and IL-13 but undetectable levels of IL-4. PBMCs from subjects with AA produced significantly larger amounts of IL-5 and IL-13 in response to IL-25 or IL-33 than from subjects with AR or HC. The prevalence of ILC2s in blood was greater in the AA group than in the AR group or the HC group. Conclusions: Innate type 2 immune responses are increased in asthma but not in AR, suggesting potential differences in the immunopathogenesis of these diseases. Peripheral blood is useful for evaluating innate type 2 immunity in humans.
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