Natural Killer Receptor 1 Dampens the Development of Allergic Eosinophilic Airway Inflammation

PLoS One. 2016 Aug 31;11(8):e0160779. doi: 10.1371/journal.pone.0160779. eCollection 2016.

Abstract

The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp) mice in comparison to OVA immunized wild type (NCR1+/+) and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL) revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils' (CCL24) and Th2 CD4+ T-cells' chemoattractants (CCL17, and CCL24) in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and decreased NCR1 ligand expression on CD11c+GR1+ cells and decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17 mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation.

MeSH terms

  • Animals
  • Antigens, Ly / genetics
  • Antigens, Ly / immunology*
  • Asthma / chemically induced
  • Asthma / genetics
  • Asthma / immunology*
  • Asthma / pathology
  • Cytokines / genetics
  • Cytokines / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Lung / immunology*
  • Lung / pathology
  • Mice
  • Mice, Transgenic
  • Natural Cytotoxicity Triggering Receptor 1 / genetics
  • Natural Cytotoxicity Triggering Receptor 1 / immunology*
  • Th2 Cells / immunology*
  • Th2 Cells / pathology

Substances

  • Antigens, Ly
  • Cytokines
  • Natural Cytotoxicity Triggering Receptor 1
  • Ncr1 protein, mouse

Grants and funding

This work was supported by the Israel Cancer Research Foundation Research Career Development Award, 4476; 5540; 3000003867; The Center for Emerging Diseases, 2506; The Israel Science Foundation, 613/04; to Yaffa Mizrachi Nebenzahl. US/Israel Binational Science Foundation, 2011123; Israel Science Foundation, 304/12; Israeli Ministry of Science and Technology/German Cancer Research Center program, CA142 to Angel Porgador. The US / Israel Bi-national Science Foundation, 2009222; 2011244; The Israel Science Foundation, 955/11; The Israel Cancer Association, 20150002; the Israel Ministry of Health, 3-10117; the Boaz and Varda Dotan Center Grant for Hemato-oncology Research to Ariel Munitz; ISEF Foundation to Shirin Elhaik Goldman. The funders/sponsors had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.