Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that IL-6 and STAT3 transcription factor-dependent upregulation of Notch4 receptor on Iung tissue regulatory T (T
reg
) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted T
reg
cells into T
H
2 and T
H
17 effector T (T
eff
) cells by Wnt and Hippo pathway-dependent mechanisms. Wnt activation induced growth and differentiation factor 15 (GDF15) expression in T
reg
cells, which activated group 2 innate lymphoid cells (ILC2) to provide a feed-forward mechanism for aggravated inflammation. Notch4, Wnt and Hippo were upregulated on circulating T
reg
cells of asthmatics as a function of disease severity, in association with reduced T
reg
cell-mediated suppression. Our studies thus identify Notch4-mediated immune tolerance subversion as a fundamental mechanism that licenses tissue inflammation in asthma.
Although evidences showed an overall reduction in outdoor air pollution levels across the globe due to COVID-19related lockdown, no comprehensive assessment was available for indoor air quality during the period of stay-at-home orders, despite that the residential indoor environment contributes most to personal exposures. We examined temporal and diurnal variations of indoor PM 2.5 based on real-time measurements from 139 indoor−outdoor co-located low-cost PurpleAir sensor sets across California for pre-, during, and post-lockdown periods in 2020 and "business-as-usual" periods in 2019. A two-step method was implemented to systematically control the quality of raw sensor data and calibrate the sensor data against co-located reference instruments. During the lockdown period, 17−24% higher indoor PM 2.5 concentrations were observed in comparison to those in the 2019 business-as-usual period. In residential sites, a clear peak in PM 2.5 concentrations in the afternoon and elevated evening levels toping at roughly 10 μg•m −3 was observed, which reflects enhanced human activity during lunch and dinner time (i.e., cooking) and possibly more cleaning and indoor movement that increase particle generation and resuspension in homes. The contribution of indoor-generated PM 2.5 to total indoor concentrations increased as high as 80% during and post-lockdown periods compared to before lockdown.
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