Thursday, July 3, 2014
Prenatal exposure to diesel exhaust induces asthma susceptibility through NK cell priming
Asthma often begins early in life and is attributed to more than just genetic factors, because the prevalence continues to rise. Epidemiological studies have indicated roles for prenatal and early childhood exposures, including exposure to diesel exhaust, however, little is known about the mechanisms involved. To elucidate this, Manners et al developed a mouse model of asthma susceptibility through prenatal exposure to diesel exhaust (J Allergy Clin Immunol 2014; 134(1): 63-72).
In this model, pregnant mice were repeatedly exposed to diesel exhaust particles (DEPs). Offspring were immunized and challenged with ovalbumin (OVA) or exposed to PBS (control) then examined for features of asthma. Compared to controls, offspring that were exposed to DEP were hypersensitive to OVA, indicated by airway hyperresponsiveness, elevated serum levels of OVA-specific IgE, and elevated levels of pulmonary and systemic T-helper type 2 (Th2) and Th17 cytokines. The authors determined that natural killer (NK) cells were the primary source of cytokine production and airway inflammation was diminished by antibody-mediated depletion of NK cells. Furthermore, asthma susceptibility was associated with increased transcription of genes known to be specifically regulated by the aryl hydrocarbon receptor (AhR) and oxidative stress.
These results coincide with previous data that suggests NK cells initiate allergic inflammation. AhR is expressed in NK cells which may provide a link between maternal exposure to diesel exhaust and asthma in offspring. Taken together, this data provides mechanistic insight into the process of prenatally-induced asthma susceptibility.