IL-15-deficient mice develop enhanced allergic responses to airway allergen exposure
| Autor: | Craig M. Schramm, Roger S. Thrall, Linda A. Guernsey, Jeffrey Rovatti, Carol A. Wu, Eric R. Secor, Jennifer Ser-Dolansky, Clinton B. Mathias, Hector L. Aguila, Sallie S. Schneider, Stephanie H. Polukort |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer medicine.medical_treatment Immunology Biology CD8-Positive T-Lymphocytes Article 03 medical and health sciences Mice 0302 clinical medicine Immune system Th2 Cells medicine Immunology and Allergy Eosinophilia Animals Interleukin-15 Mice Knockout Innate immune system respiratory system Allergens Natural killer T cell Asthma 030104 developmental biology Cytokine Interleukin 15 Natural Killer T-Cells medicine.symptom CD8 030215 immunology |
| Zdroj: | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 47(5) |
| ISSN: | 1365-2222 |
| Popis: | Background Interleukin-15 is a pleiotropic cytokine that is critical for the development and survival of multiple hematopoietic lineages. Mice lacking IL-15 have selective defects in populations of several pro-allergic immune cells including natural killer (NK) cells, NKT cells, and memory CD8+T cells. We therefore hypothesized that IL-15-/- mice will have reduced inflammatory responses during the development of allergic airway disease (AAD). Objective To determine whether IL-15-/- mice have attenuated allergic responses in a mouse model of AAD. Methods C57BL/6 wild-type (WT) and IL-15-/- mice were sensitized and challenged with ovalbumin (OVA) and the development of AAD was ascertained by examining changes in airway inflammatory responses, Th2 responses, and lung histopathology. Results Here we report that IL-15-/- mice developed enhanced allergic responses in an OVA-induced model of AAD. In the absence of IL-15, OVA-challenged mice exhibited enhanced bronchial eosinophilic inflammation, elevated IL-13 production, and severe lung histopathology in comparison with WT mice. In addition, increased numbers of CD4+T and B cells in the spleens and broncholaveolar lavage (BAL) were also observed. Examination of OVA-challenged IL-15Rα-/- animals revealed a similar phenotype resulting in enhanced airway eosinophilia compared to WT mice. Adoptive transfer of splenic CD8+T cells from OVA-sensitized WT mice suppressed the enhancement of eosinophilia in IL-15-/- animals to levels observed in WT mice, but had no further effects. Conclusion and Clinical Relevance These data demonstrate that mice with an endogenous IL-15 deficiency are susceptible to the development of severe, enhanced Th2-mediated AAD, which can be regulated by CD8+T cells. Furthermore, the development of disease as well as allergen-specific Th2 responses occurs despite deficiencies in several IL-15-dependent cell types including NK, NKT, and γδ T cells, suggesting that these cells or their subsets are dispensable for the induction of AAD in IL-15-deficient mice. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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