Journal Article

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

Moshkovits, Itay, Vronov, Elena, Apte, Ron N., Munitz, Ariel, Karo-Atar, Danielle, Filiba, Ayelet, Tsirulsky, Yevgeny, Dagan, Ron, Shagan, Marilou, Mizrachi Nebenzahl, Yaffa, Elhaik Goldman, Shirin, Shemesh, Avishai, Benharroch, D aniel, Porgador, Angel

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Airway obstruction / Allergies / Alveoli / Analysis / Animals / Antigens / Antigens, Ly - genetics / Antigens, Ly - immunology / Asthma / Asthma - chemically induced / Asthma - genetics / Asthma - immunology / Asthma - pathology / Biology and Life Sciences / Blood & organ donations / Bronchoalveolar lavage / Bronchus / CCL17 protein / CD11c antigen / CD4 antigen / Chemokines / Chemotactic factors / Complications and side effects / Cytokines / Cytokines - genetics / Cytokines - immunology / Cytotoxicity / Dendritic cells / Disease / Eosinophils / Gene expression / Gene Expression Regulation - genetics / Gene Expression Regulation - immunology / Hypersensitivity / Immunization / Immunoglobulin E / Immunology / Infiltration / Inflammation / Interleukin 13 / Interleukin 17 / Interleukin 4 / Interleukin 6 / Killer cells / Leukocytes (eosinophilic) / Leukocytes (granulocytic) / Leukocytes (mononuclear) / Lung - immunology / Lung - pathology / Lungs / Lymphocyte receptors / Lymphocytes / Lymphocytes T / Macrophages / Medicine / Medicine and Health Sciences / Mice / Mice, Transgenic / Natural Cytotoxicity Triggering Receptor 1 - genetics / Natural Cytotoxicity Triggering Receptor 1 - immunology / Preservation / Research and Analysis Methods / Respiratory tract / Respiratory tract diseases / Risk factors / T cell receptors / Th2 Cells - immunology / Th2 Cells - pathology / Tumor necrosis factor-α