Particulate matter-shaped Th17 cell plasticity impairs the colonic mucus layer

The intestine is one of the target organs upon ambient particulate matter (PM) exposure. However, the mechanism underlying PM-induced colonic injury remains unexplained. The present study emphasizes the significance of adaptive T cells crossing circulation-intestine signaling during PM exposure. To investigate this, mononuclear cells in circulation and intestine were isolated and exposed to PM ex vivo. We found that the PM-induced peripheral inflammatory microenvironment promoted inflammatory polarization of T helper 17 (Th17) cells in circulation and intestine in sequence. Further animal models and the Th17 cell adoptive transfer model showed that PM exposure induced the loss of colonic mucus through priming inflammatory Th17 cells in vivo. Mechanistically, PM exposure activated aryl hydrocarbon receptor (AhR) signaling and transcriptionally induced retinoic acid receptor-related orphan receptor C (RORC) expression in circulation Th17 cells, subsequently activating and polarizing colonic Th17 cells, ultimately resulting in the loss of colonic mucus. Moreover, Interleukin (IL)-6 knockout resisted PM exposure-induced colonic injury via inhibiting differentiation of Th17 cells. To conclude, the study results provide clarification on the processes of PM-related immunology response in the colon and the mechanism aiding the development of novel intervention strategies to maintain homeostasis in the colon.