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

Area of Science:

• Immunology
• Environmental Health
• Gastroenterology

Background:

• The intestine is susceptible to ambient particulate matter (PM) exposure.
• Mechanisms of PM-induced colonic injury are not fully understood.
• Adaptive T cell signaling between circulation and the intestine is implicated.

Purpose of the Study:

• To elucidate the mechanism of PM-induced colonic injury.
• To investigate the role of T helper 17 (Th17) cells in PM exposure.
• To identify the signaling pathways involved in PM-related colonic immune responses.

Main Methods:

• Isolation and ex vivo exposure of mononuclear cells from circulation and intestine to PM.
• Utilizing animal models and Th17 cell adoptive transfer models.
• Investigating aryl hydrocarbon receptor (AhR) and retinoic acid receptor-related orphan receptor C (RORC) signaling pathways.

Main Results:

• PM exposure promotes inflammatory polarization of Th17 cells in circulation and the intestine.
• PM induces colonic mucus loss by priming inflammatory Th17 cells.
• PM activates AhR signaling and RORC expression in Th17 cells, leading to colonic Th17 cell activation and mucus loss.
• Interleukin-6 (IL-6) knockout protects against PM-induced colonic injury by inhibiting Th17 cell differentiation.

Conclusions:

• PM exposure triggers a specific immune response in the colon involving Th17 cell polarization.
• The study clarifies the mechanism of PM-induced colonic injury via circulation-intestine Th17 cell signaling.
• Findings offer insights for developing interventions to maintain colonic homeostasis.