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Identification of a PD-L1+Tim-1+ iNKT subset that protects against fine particulate matter-induced airway
Christina Li-Ping Thio1, Alan Chuan-Ying Lai1, Jo-Chiao Wang1
1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Abstract:
Although air pollutants such as fine particulate matter (PM2.5) are associated with acute and chronic lung inflammation, the etiology of PM2.5-induced airway inflammation remains poorly understood. Here we report that PM2.5 triggered airway hyperreactivity (AHR) and neutrophilic inflammation with concomitant increases in Th1 and Th17 responses and epithelial cell apoptosis. We found that γδ T cells promoted neutrophilic inflammation and AHR through IL-17A. Unexpectedly, we found that invariant natural killer T (iNKT) cells played a protective role in PM2.5-induced pulmonary inflammation. Specifically, PM2.5 activated a suppressive CD4- iNKT cell subset that coexpressed Tim-1 and programmed cell death ligand 1 (PD-L1). Activation of this suppressive subset was mediated by Tim-1 recognition of phosphatidylserine on apoptotic cells. The suppressive iNKT subset inhibited γδ T cell expansion and intrinsic IL-17A production, and the inhibitory effects of iNKT cells on the cytokine-producing capacity of γδ T cells were mediated in part by PD-1/PD-L1 signaling. Taken together, our findings underscore a pathogenic role for IL-17A-producing γδ T cells in PM2.5-elicited inflammation and identify PD-L1+Tim-1+CD4- iNKT cells as a protective subset that prevents PM2.5-induced AHR and neutrophilia by inhibiting γδ T cell function.
Insights
Fine particulate matter (PM2.5) causes lung inflammation via IL-17A-producing γδ T cells. Suppressive invariant natural killer T (iNKT) cells protect against PM2.5-induced airway hyperreactivity and inflammation.
Area of Science:
- Immunology
- Environmental Health
- Pulmonology
Background:
- Air pollutants like fine particulate matter (PM2.5) are linked to lung inflammation.
- The precise mechanisms driving PM2.5-induced airway inflammation are not fully understood.
Purpose of the Study:
- To elucidate the cellular and molecular pathways involved in PM2.5-induced airway inflammation.
- To identify key immune cell populations and signaling pathways mediating or protecting against PM2.5-induced lung injury.
Main Methods:
- Investigated PM2.5 effects on mouse models, focusing on T cell responses (γδ T cells, iNKT cells) and airway hyperreactivity.
- Utilized flow cytometry and cytokine analysis to assess immune cell activation and function.
- Examined the role of Tim-1 and PD-1/PD-L1 signaling in iNKT cell-mediated regulation.
Main Results:
- PM2.5 exposure induced airway hyperreactivity, neutrophilic inflammation, and Th1/Th17 responses.
- γδ T cells promoted inflammation and airway hyperreactivity via IL-17A.
- A suppressive CD4- iNKT cell subset (Tim-1+, PD-L1+) inhibited γδ T cell expansion and IL-17A production, protecting against PM2.5-induced lung inflammation.
Conclusions:
- IL-17A-producing γδ T cells play a pathogenic role in PM2.5-induced lung inflammation.
- CD4- iNKT cells expressing Tim-1 and PD-L1 act as a protective immune subset by suppressing γδ T cell activity.
- Targeting iNKT cell pathways may offer therapeutic strategies for PM2.5-related respiratory diseases.
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