Natural Killer Cells in Asthma

Abstract

The worldwide prevalence, morbidity, and mortality of asthma have dramatically increased over the last few decades and there is a clear need to identify new effective therapeutic and prophylactic strategies. Despite high numbers of NK cells in the lung and their ability to generate a variety of immunomodulatory mediators, the potential of NK cells as therapeutic targets in allergic airway disease has been largely overlooked. The fact that IgE, acting through FcγRIII, can activate NK cells resulting in cytokine/chemokine production implies that NK cells may contribute to IgE-mediated allergic responses. Indeed, current evidence suggests that NK cells can promote allergic airway responses during sensitization and ongoing inflammation. In animal models, increased NK cells are observed in the lung following antigen challenge and depletion of the cells before immunization inhibits allergic airway inflammation. Moreover, in asthmatics, NK cell phenotype is altered and may contribute to the promotion of a pro-inflammatory Th2-type environment. Conversely, driving NK cells toward an IFN-γ-secreting phenotype can reduce features of the allergic airway response in animal models. However, we have limited knowledge of the signals that drive the development of distinct subsets and functional phenotypes of NK cells in the lung and thus the role and therapeutic potential of NK cells in the allergic airway remains unclear. Here we review the potentially diverse role of NK cells in allergic airway disease, identify gaps in current knowledge, and discuss the potential of modulating NK cell function as a treatment strategy in asthma.

Respiratory Viruses and Asthma

“…123 However, when NK cell responses are impaired to viral infection, reduced levels of IFNγ may promote type 2 immune environment in the lungs with increased inflammation, viral replication, and clinical features of asthma. 124,125 Interestingly, impaired NK cell responses appear to be a strong feature of acute severe RSV bronchiolitis, 126 and as we have previously discussed, this is an independent predictor for recurring wheeze up to the age of 6 years.…”

PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen

“…Previous reports studying the impact of NK cells on the development of allergic lung inflammation have yielded contradictory findings. In certain instances, NK cells inhibited allergic lung inflammation (14, 15) and in others they promoted eosinophilic inflammation (16, 53) reviewed in (54). In some studies, the antigen sensitization phase was more susceptible to NK cell-mediated regulation compared to the subsequent lung inflammatory response elicited by OVA inhalation (55).…”

Innate immunity is a key factor for the resolution of inflammation in asthma

“…NK cells serve essential roles in host defence, including cytokine secretion, contact-dependent cell–cell signalling and direct killing of other immune cells, and are involved in combating tumours, viral infections, parasites and bacteria [ 99 ]. Roles for NK cells in asthma and allergic diseases are undefined and both disease-promoting and disease-controlling functions have been suggested [ 100 ].…”