IL-5 production by NK cells contributes to eosinophil infiltration in a mouse model of allergic inflammation.
IL-5 production in vivo plays a unique role in the production, activation, and localization of eosinophils in a variety of allergic conditions. The current paradigm suggests that allergen-specific Th2 cells are the main source for the IL-5 production. The experiments outlined in this work, however, suggest that in vivo production of IL-5 by NK cells can separately influence eosinophil-associated inflammatory responses. Specifically, a mouse model of allergic inflammation was used in which C57BL/6 mice were immunized and challenged with a short ragweed Ag extract, known to induce a selective eosinophilia within the peritoneal cavity. Peritoneal lavage fluids from these mice also contained increased numbers of T cells and NK cells, as well as significantly elevated levels of IL-4, IL-5, and IFN-gamma. Flow-cytometric analysis of cytokine-producing cells in peritoneal lavage fluid revealed increased numbers of IL-5-producing cells in both T cell and NK cell populations following allergen exposure. Depletion of NK cells by treatment with NK1.1 Abs selectively reduced the number of infiltrating eosinophils by more than 50%. Moreover, the inhibition of the infiltration of eosinophils was accompanied by a complete loss of IL-5-producing NK cells and significantly reduced levels of peritoneal lavage fluid IL-5, whereas the number of IL-5-producing T cells was not affected. Thus, the results presented in this study provide clear evidence for a novel immunoregulatory function of NK cells in vivo, promoting allergen-induced eosinophilic inflammatory responses by the production of IL-5.
Mayo Clinic, Department of Immunology, Rochester, MN 55902, USA. christoph.walker@pharma.novartis.com
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Walker
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Checkel
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Cammisuli
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Leibson
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Gleich
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001202:Ascitic Fluid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007275:Injections, Intravenous; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D010533:Peritoneal Lavage; D010538:Peritonitis / Q000276:immunology* / Q000473:pathology; D011058:Pollen / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism
D000485:Allergens; D000911:Antibodies, Monoclonal; D015848:Interleukin-5