Background
Long-term exposure to fine particulate matter (PM2.5) increases susceptibility to chronic respiratory diseases, including inflammation and interstitial fibrosis. However, the regulatory mechanisms by which the immune response mediates the initiation of pulmonary fibrosis has yet to be fully characterized. This study aimed to illustrate the interplay between different cell clusters and key pathways in triggering chronic lung injuries in mice following PM exposure.
Results
Six-week-old C57BL/6J male mice were exposed to PM or filtered air for 16 weeks in a real-ambient PM exposure system in Shijiazhuang, China. The transcriptional profiles of whole lung cells following sub-chronic PM exposure were characterized by analysis of single-cell transcriptomics. The IL-17A knockout (IL-17A−/−) mouse model was utilized to determine whether the IL-17 signaling pathway mediated immune dysregulation in PM-induced chronic lung injuries. After 16-week PM exposure, chronic lung injuries with excessive collagen deposition and increased fibroblasts, neutrophils, and monocytes were noted concurrent with a decreased number of major classes of immune cells. Single-cell analysis showed that activation of the IL-17 signaling pathway was involved in the progression of pulmonary fibrosis upon sub-chronic PM exposure. Depletion of IL-17A led to significant decline in chronic lung injuries, which was mainly triggered by reduced recruitment of myeloid-derived suppressor cells (MDSCs) and downregulation of TGF-β.
Conclusion
These novel findings demonstrate that immunosuppression via the IL-17A pathway plays a critical role in the initiation of chronic lung injuries upon sub-chronic PM exposure.
Paleoearthquake data obtained from fault trenching are essential for rebuilding the rupture history and understanding the rupture behavior of active faults. However, due to the lack of attention to stratigraphic sequences, the usual multiple trench constraining method may result in uncertainties of paleoearthquake sequences. In this study, we proposed an improved constraining method to generate stratigraphic sequences from multiple trenches of different drainages to obtain a paleoearthquake sequence of the Gulang fault. Single-trench stratigraphic sequences were built up by nineteen trenches excavated along the fault. Based on stratigraphic characteristics, we found the strata sedimented around the fault were derived from five drainages. The single-trench sequences were divided into five drainages to establish the composite sequence of multiple trenches through the correlation of stratigraphic units. Meanwhile, we used high-quality event indicators to pick out very likely earthquakes. Coupled with the dating samples, the events were used to determine the earthquake horizons in the composite sequence and to constrain the numbers and ages of events in each drainage. After combining the event sequences, six paleoearthquakes were determined along the Gulang fault since the late Pleistocene. Their occurrence timings are 13,700–10,400, 10,400–10,200, 8,560–7,295, 5,825–4,810, 4,285–3,200, and 2,615–2,240 a B.P. And their different rupture scenarios indicate that the fault might be composed of two rupture segments.
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