IL-23 contributes to Particulate Matter induced allergic asthma in the early life of mice and promotes asthma susceptibility.

Abstract

Air pollutant exposure leads to and exacerbates respiratory diseases. Particulate Matter (PM) is a major deleterious factor in the pathophysiology of asthma. Nonetheless, studies on the effects and mechanisms of exposure in the early life of mice remain unresolved. This study aimed to investigate changes in allergic phenotypes and effects on allergen-specific memory T cells resulting from co-exposure of mice in the early life to PM and house dust mites (HDM) and to explore the role of interleukin-23 (IL-23) in this process. PM and low-dose HDM were administered intranasally in 4-day-old C57BL/6 mice. After confirming an increase in IL-23 expression in mouse lung tissues, changes in the asthma phenotype and lung effector/memory Th2 or Th17 cells were evaluated after intranasal administration of anti-IL-23 antibody (Ab) during co-exposure to PM and HDM. Evaluation was performed up to 7weeks after the last administration. Co-exposure to PM and low-dose HDM resulted in increases in airway hyperresponsiveness (AHR), eosinophils, neutrophils, and persistent Th2/Th17 effector/memory cells, which were all inhibited by anti-IL-23 Ab administration. When low-dose HDM was administered twice after a 7-week rest, mice exposed to PM and HDM during the previous early life period exhibited re-increases AHR, eosinophil count, HDM-specific IgG1, and effector/memory Th2 and Th17 cell populations. However, anti-IL-23 Ab administration during the early life period resulted in inhibition. Co-exposure to PM and low-dose HDM reinforced the allergic phenotypes and allergen-specific memory responses in early life of mice. During this process, IL-23 contributes to the enhancement of effector/memory Th2/Th17 cells and allergic phenotypes. KEY MESSAGES: PM-induced IL-23 expression, allergic responses in HDMinstilled mice of early life period. PM-induced effector/memory Th2/Th17 cells in HDMinstilled mice of early life period. Inhibition of IL-23 reduced the increase in allergic responses. Inhibition of IL-23 reduced the increase in allergic responses. After the resting period, HDM administration showed re-increase in allergic responses. Inhibition of IL-23 reduced the HDM-recall allergic responses.