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Activation of invariant NKT cells in regional lymph nodes as new antigen-specific immunotherapy via induction of IL-21 and IFN-γ
MedLine Citation:
PMID:  24943738     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Invariant natural killer T (iNKT) cells play important immunoregulatory functions in allergen-induced airway hyperresponsiveness and inflammation. To clarify the role of iNKT cells in allergic rhinitis (AR), we generated bone marrow-derived dendritic cells (BMDCs), which were pulsed by OVA and α-galactosylceramide (OVA/α-GalCer-BMDCs) and administered into the oral submucosa of OVA-sensitized mice before nasal challenge. Nasal symptoms, level of OVA-specific IgE, and Th2 cytokine production in cervical lymph nodes (CLNs) were significantly ameliorated in wild type (WT) mice treated with OVA/α-GalCer-BMDCs, but not in WT mice treated with OVA-BMDCs. These anti-allergic effects were not observed in Jα18(-/-) recipients that lack iNKT cells, even after similar treatment with OVA/α-GalCer-BMDCs in an adoptive transfer study with CD4(+) T cells and B cells from OVA-sensitized WT mice. In WT recipients of OVA/α-GalCer-BMDCs, the number of IL-21-producing iNKT cells increased significantly and the Th1/Th2 balance shifted toward the Th1 dominant state. Treatment with anti-IL-21 and anti-IFN-γ antibodies abrogated these anti-allergic effects in mice treated with α-GalCer/OVA-BMDCs. These results suggest that activation of iNKT cells in regional lymph nodes induces anti-allergic effects through production of IL-21 or IFN-γ, and that these effects are enhanced by simultaneous stimulation with antigen. Thus, iNKT cells might be a useful target in development of new treatment strategies for AR.
Authors:
Toshioki Sakurai; Ayako Inamine; Tomohisa Iinuma; Urara Funakoshi; Syuji Yonekura; Daiju Sakurai; Toyoyuki Hanazawa; Toshinori Nakayama; Yasuyuki Ishii; Yoshitaka Okamoto
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-18
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  -     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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