The human immune system responds in two main ways to the presence of pathogens and foreign objects: the type 1 response involves the use of white blood cells to destroy pathogens, while the type 2 response involves the production of antibodies to fight infection. Allergies and asthma are the result of a hyperreactive type 2 immune response, but their initial triggers have not yet been pinpointed. This study’s findings shed light on the process of allergy development early in life, demonstrating that immune cells gather in the lungs of newborns because of the protein IL-33, which also promotes long-term immunity.
Identifying key drivers of early life allergic response
Using mice as models, the researchers investigated immune response to house dust mites by exposing newborn mice to the allergen first to sensitize them, and then again to provoke an immune response. They were surprised to observe that mice sensitized to house dust mites on day 14 after birth showed greater type 2 immune responses when exposed again to the allergen than adult mice, mice exposed on day 3.
Prof. Bart Lambrecht (VIB-UGent): “We identified day 14 after birth as the point at which there were more type 2 immune cells present in the neonatal lung than in the adult lung, and we observed that these cells were producing more of the protein interleukin-33. Mice without the IL-33 receptor showed a much smaller type 2 immune response. Even further, if mice exposed to house dust mites on day 14 were simultaneously given a decoy receptor that binds to IL-33, the resulting type 2 immune response to the second house dust mite exposure was much smaller. This underlines IL-33’s role in immunity in these newborn mice.”
These results are even more surprising, considering the fact that newborn mice have very few dendritic cells compared with adult mice. Dendritic cells, which are present in any organ with contact with the outside environment of the body, are immune cells that move pathogens and other foreign materials to white blood cells, which destroy them (type 1 immunity) and subsequently trigger type 2 immunity.
Prof. Bart Lambrecht: “We have evidence that type 2 immunity in newborn mice is heavily dependent on IL-33 and not on white blood cells, and that IL-33 enhances the function of immunity-boosting dendritic cells in the newborn lung. Although there aren’t many dendritic cells in postnatal lungs, they appear to be very efficient at promoting long-term type 2 immunity.”
Translating insights into human applications
Early type 2 immune response to house dust mites has been proven to be a major risk factor for the development of asthma in children, but the reason why children are more at risk than adults has remained elusive. This is also complicated by the fact that the lungs and immune systems of young children undergo extensive changes during the first few years of life.
Prof. Bart Lambrecht: “The results of our study show that IL-33 is a driver of asthma development in neonates that changes the way immune cells communicate with each other. As asthma is a common and sometimes fatal immune disorder to young children, information relating to underlying causes or triggers of the disease could prove critical to therapies that treat it, or even prevent its emergence.”
Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung, de Kleer et al., Immunity 2016
This work was also covered in a Research Highlight of Nature reviews of Immunology.
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