CARD9-mediated ambient PM_2.5-induced pulmonary injury is associated with Th17 cell

Area of Science:

• Environmental Health
• Immunology
• Toxicology

Background:

• Particulate matter (PM_2.5) exposure is a significant risk factor for pulmonary injury, linked to inflammation and oxidative stress.
• Caspase recruitment domain (CARD) 9 is implicated in inflammatory responses, but its specific role in PM_2.5-induced lung damage requires elucidation.

Purpose of the Study:

• To investigate the role of CARD9 in ambient PM_2.5-induced pulmonary injury in a mouse model.
• To analyze the impact of CARD9 deficiency on immune cell populations and inflammatory markers in the lungs and spleen following PM_2.5 exposure.

Main Methods:

• Caspase recruitment domain (CARD) 9 knockout (CARD9^-/-) and wild-type (C57BL/6) mice were exposed to varying doses of PM_2.5 via intratracheal instillation.
• Pulmonary tissue, bronchoalveolar lavage fluid (BALF), and spleen were collected post-exposure for histological examination and analysis of immune cell populations and cytokine levels.
• Gene and protein expression of key inflammatory markers, including IL-17A, IL-6, RORγt, Foxp3, and NF-κB, were assessed.

Main Results:

• PM_2.5 exposure led to inflammatory cell infiltration and alveolar septal thickening in mouse lungs.
• CARD9^-/- mice exhibited significantly higher regulatory T (Treg) cells and lower T helper 17 (Th17) cells in the spleen compared to wild-type mice.
• Lower levels of IL-6 and IL-17A in BALF, and reduced mRNA expression of IL-17A, IL-6, and RORγt, along with higher Foxp3 mRNA levels, were observed in CARD9^-/- mice.
• Nuclear factor κB (NF-κB) protein expression was elevated in wild-type mice compared to CARD9^-/- mice.

Conclusions:

• Ambient PM_2.5-induced pulmonary injury is associated with immune and inflammatory responses.
• CARD9 plays a crucial role in mediating Th17/Treg cell differentiation, suggesting it is a key factor in PM_2.5-induced pulmonary damage.