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

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.

The acute pulmonary toxicity in mice induced by <i>Staphylococcus aureus</i>, particulate matter, and their combination

“…Meanwhile, increased production of IgE in serum of mice exposed to S. aureus or the combination of PM and S. aureus correlated positively with the upregulated Th2 cytokine production. Several studies reported that the development of allergic airway inflammation and bronchial asthma was associated with elevated IgE levels, the predominance of Th2 cytokine production, and eosinophils related-inflammation of the airways [7, 26].…”

The Natural Cytotoxicity Receptors in Health and Disease

“…These results suggested that NKp46 signaling enhances allergic responses. In contrast, a separate study using a delayed type I hypersensitivity model, showed that NKp46 signaling suppressed the development of airway eosinophilia following intranasal OVA challenge (179). It will be interesting to see which NKp46-expressing cell types, such as NK cells, ILC1 or ILC3, might be responsible for either suppressing (179) or augmenting (178) airway inflammation in models of type I and type IV hypersensitivity, respectively.…”

Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis

“…It should be noted, however, that also transgenic mice exist which specifically react to more relevant allergens, like the 1-DER mice expressing the T-cell receptor specific for the major house dust mite allergen Der p 1 from Dermatophagoides pteronyssinus [ 16 ]. Recent reports, all using ovalbumin have shown aggravation of asthma by pentraxin 3 [ 17 ], prostaglandin E2 [ 18 ], IL-15-deficiency [ 19 ] or suppression of asthma by anti-inflammatory protein 2 from hookworms [ 20 ▪▪ ], natural killer (NK) receptor 1 [ 21 ] and inhibition of hypoxia inducible factor-1α [ 22 ]. Sensitization with ovalbumin was usually performed by the intraperitoneal route, which, though valid, hardly represents the natural respiratory sensitization process in humans or animals.…”