Journal Article

Role of NKp46+ natural killer cells in house dust mite‐driven asthma

Boon, Louis, Vivier, Eric, Lambrecht, Bart N, van Moorleghem, Justine, van Helden, Mary J, Hammad, Hamida, Haspeslagh, Eline, Deswarte, Kim, De Prijck, Sofie

2018

Overview

House dust mite (HDM)‐allergic asthma is driven by T helper 2 (Th2) lymphocytes, but also innate immune cells control key aspects of the disease. The precise function of innate natural killer (NK) cells during the initiation and propagation of asthma has been very confusing, in part because different, not entirely specific, strategies were used to target these cells. We show that HDM inhalation rapidly led to the accumulation of NK cells in the lung‐draining lymph nodes and of activated CD69 + NK cells in the bronchoalveolar lumen. However, genetically engineered Ncr1 ‐DTA or Ncr1 ‐DTR mice that constitutively or temporarily lack NK cells, still developed all key features of acute or chronic HDM‐driven asthma, such as bronchial hyperreactivity, Th2 cytokine production, eosinophilia, mucus overproduction, and Th2‐dependent immunoglobulin serum titers. The same results were obtained by administration of conventional NK1.1 or asialo‐GM1 NK cell‐depleting antibodies, antibody‐mediated blocking of the NKG2D receptor, or genetic NKG2D deficiency. Thus, although NK cells accumulate in allergen‐challenged lungs, our findings comprehensively demonstrate that these cells are not required for HDM‐driven asthma in the mouse. Synopsis The function of NK cells in allergic asthma development has been confusing, as targeting strategies with different specificities have generated conflicting results. Here, conventional NK cells are genetically and specifically depleted and shown to be dispensable for asthma development in mice. Allergic asthma to house dust mite or ovalbumin can be induced in genetically engineered Ncr1‐DTA mice that constitutively lack all NKp46 + cells. The asthma phenotype is neither affected by temporarily depleting NK cells in Ncr1‐DTR mice, nor by antibody‐mediated depletion of NK1.1 + or asialoGM1 + cells. Antibody‐mediated blocking or genetic depletion of the NKG2D receptor does not influence allergic asthma development. Graphical Abstract The function of NK cells in allergic asthma development has been confusing, as targeting strategies with different specificities have generated conflicting results. Here, conventional NK cells are genetically and specifically depleted and shown to be dispensable for asthma development in mice.

• Publisher: Nature Publishing Group UK,EMBO Press,Wiley Open Access,John Wiley and Sons Inc,Springer Nature
• Subject: Allergens / allergic asthma / Alveoli / Animals / Antigens, Ly - metabolism / Asthma / Asthma - metabolism / Bronchus / CD69 antigen / Dust / EMBO19 / EMBO35 / Eosinophilia / Female / Genetic engineering / house dust mite / Immunology / Inhalation / Killer Cells, Natural - metabolism / Life Sciences / Lymph nodes / Lymphocyte receptors / Lymphocytes T / Male / Mice / Mice, Inbred C57BL / Natural Cytotoxicity Triggering Receptor 1 - metabolism / Natural killer cells / NK Cell Lectin-Like Receptor Subfamily K - genetics / NK Cell Lectin-Like Receptor Subfamily K - metabolism / NK cells / NKG2 antigen / NKG2D / NKp46 / Ovalbumin / Phenotypes / Pyroglyphidae - immunology / Research Article