CARD9-mediated ambient PM2.5-induced pulmonary injury is associated with Th17 cell

Abstract

Inflammation and oxidative stress are important risk factors in PM_2.5-induced injury. The current study attempted to study the role of caspase recruitment domain (CARD) 9 in ambient PM_2.5-induced pulmonary injury in mice. The CARD9^-/- and C57BL/6 mice were exposed to 3.6, 7.8 and 15.6mg/kgbw of PM_2.5 or saline by intratracheal instillation. After the last PM_2.5 exposure, the spleen, bronchoalveolar lavage fluid (BALF) and pulmonary tissue were collected and examined. The results showed that PM_2.5 exposure induced inflammatory cell infiltration and alveolar septal thickening in the lung. Regulatory T (Treg) cells in spleen of CARD9^-/- mice were significantly higher than that in the C57BL/6 mice, whereas the T helper cells 17 (Th17) were lower. The levels of interleukin (IL)-6 and IL-17A in BALF of the CARD9^-/- mice were significantly lower than that in the C57BL/6 mice. The mRNA expression of IL-17A, IL-6 and RORγt in the lung of the CARD9^-/- mice is significantly lower than that in the C57BL/6 mice, whereas the mRNA levels of Foxp3 in CARD9^-/- mice were significantly higher than that in the C57BL/6 mice at the same dose of PM_2.5. The protein expression of nuclear factor κB (NF-κB) is higher in the C57BL/6 mice than that in the CARD9^-/- mice. This study indicates that ambient PM_2.5-induced pulmonary injury is associated with the immune and inflammatory response. CARD9-mediated Th17/Treg differentiation probably played an important role in PM_2.5-induced pulmonary damage.

Keywords: CARD9; Fine particulate matter; Inflammation; Th17.