title: IL-15-deficient mice develop enhanced allergic responses to airway allergen exposure.
abstract: BACKGROUND
  Interleukin-15 is a pleiotropic cytokine that is critical for the development and survival of multiple haematopoietic 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 bronchoalveolar 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA, USA.
authors.forename: C B
authors.identifier: http://orcid.org/0000-0002-0223-4842
authors.initials: CB
authors.lastname: Mathias
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Schramm
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Guernsey
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Polukort
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rovatti
authors.affiliation: Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ser-Dolansky
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: E
authors.initials: E
authors.lastname: Secor
authors.affiliation: Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Schneider
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Thrall
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Aguila
mesh_terms: D000485:Allergens / Q000633:toxicity*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019409:Interleukin-15 / Q000172:deficiency* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D019409:Interleukin-15
keywords: asthma; basic mechanisms; innate immunity