Air pollution mediates diabetes by disrupting gut innate mucosal immunity

Abstract

15Air pollution has emerged as an unexpected risk factor for diabetes 1-6 . The mechanisms 16 linking air pollution and diabetes remain, however, unknown. It has been postulated 17 that lung exposure mediates diabetes via systemic inflammation and insulin resistance 7-9 . 18 By contrast, gut exposure to pollutants has received little attention, even though a large 19 proportion of air pollution particles are swallowed after mucociliary clearance from the 20 upper airways 10 . Here, we identified intestinal macrophages as key mediators linking air 21 pollutants with impaired beta-cell function. Upon oral exposure to air pollution, 22 intestinal macrophages up-regulated inflammatory-and interferon-response pathways, 23 which disrupted their normal differentiation towards an anti-inflammatory/resident 24 phenotype. The resulting pro-inflammatory milieu in the gut impaired beta-cell identity 25