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Published on: January 19, 2019
PM2.5 affects establishment of immune tolerance in newborn mice by reducing PD-L1 expression
L I Yan1, Caihui Gong, Linyan Ying
1Department of Respiration Center, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People's Republic of China.
Abstract:
This study was conducted to determine whether exposure to particulate matter 2.5 (PM2.5) affects the immune tolerance of neonatal mice via the regulation of PD-L1 expression. One-week-old BALB/c mice were exposed to PM2.5 for 8 days. From day 8 to day 18, the mice were treated with 5 μg house dust mite (HDM) (i. n.) every two days. Adenovirus-carried PD-L1 overexpression vectors were infected into mice via nasal inhalation 6 days after exposure to PM2.5. Airway hyperresponsiveness (AHR) was examined in mice 19 days after exposure to PM2.5, and the related parameters of airway inflammation were studied on day 22. Co-exposure to PM2.5 and HDM reduced PD-L1 expression but greatly increased infiltration of inflammatory cells, which was reversed by PD-L1 overexpression. Co-exposure to PM2.5 and HDM also elevated serum IL-4, IL-5 and IL-13 levels and reduced TGF-β level. Exposure to PM2.5 alone slightly increased the numbers of dendritic cells (DCs) but reduced the numbers of antigen-presenting cells expressing PD-L1 and Treg cells. Therefore, early exposure to PM2.5 reduced PD-L1 expression in the lungs of neonatal mice, which interfered with immune tolerance establishment and subsequently resulted in allergic airway inflammation.
Insights
Early exposure to particulate matter 2.5 (PM2.5) impairs immune tolerance in neonatal mice by reducing PD-L1 expression, leading to allergic airway inflammation. This highlights PM2.5
Area of Science:
- Immunology
- Environmental Health
- Respiratory Medicine
Background:
- Neonatal immune tolerance is crucial for preventing allergies.
- Particulate matter 2.5 (PM2.5) exposure is a growing environmental concern.
- The role of PD-L1 in PM2.5-induced immune dysregulation is not fully understood.
Purpose of the Study:
- To investigate the effect of PM2.5 exposure on PD-L1 expression in neonatal mice.
- To determine if PM2.5 exposure impacts immune tolerance development.
- To explore the link between PM2.5, PD-L1, and allergic airway inflammation.
Main Methods:
- Neonatal BALB/c mice were exposed to PM2.5 and house dust mite (HDM).
- PD-L1 overexpression vectors were administered via nasal inhalation.
- Airway hyperresponsiveness, inflammatory cell infiltration, cytokine levels, and immune cell populations were analyzed.
Main Results:
- Co-exposure to PM2.5 and HDM reduced PD-L1 expression and increased airway inflammation.
- PD-L1 overexpression reversed the inflammatory effects of PM2.5 and HDM.
- PM2.5 exposure alone decreased PD-L1 expressing cells and regulatory T cells (Tregs).
Conclusions:
- Early-life PM2.5 exposure downregulates lung PD-L1 expression in neonatal mice.
- This downregulation disrupts immune tolerance and promotes allergic airway inflammation.
- Targeting PD-L1 may offer a therapeutic strategy for PM2.5-induced allergies.
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