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. 2022 Nov 30;5:100177. doi: 10.1016/j.jtauto.2022.100177

Fig. 2.

Fig. 2

The mechanisms of polycyclic aromatic hydrocarbons on human immune cells.

PAHs contact mainly with the skin and respiratory tract, and tend to be concentrated in the skin and bronchial epithelial cells. Due to the high lipophilicity of PAHs, they readily penetrate the epithelial barrier, accumulate slowly in fat, and eventually persist for a long time.

In general, AhR signaling is needed in both adaptive and innate immune cells, in addition to different intracellular mechanisms, including cytochrome P450 (CYP)- reactive oxygen species (ROS) axis and intracellular calcium mobilization. The study of epigenetic mechanisms has also become increasingly diverse.

(1) PAHs can induce Th17 differentiation. The possible intracellular mechanisms include the Ahr-Jag1-Notch signaling pathway and the involvement of the glycogenesis regulator Hif-1α. The secretion of Th17 cytokines, including IL-17 and IL-22, was also increased. Th17 cells can be transformed by AhR into type 1 T regulatory (Tr1) cells that produce the immunosuppressive cytokine IL-10. Conversely, in Tr1 cells, IL-27 was able to increase the AhR expression through a Stat3-driven mechanism.

(2) PAH exposure is associated with impaired Treg function, downregulation of Foxp3, and increased methylation in the Foxp3 promoter region. PM2.5 promotes the expression of Got1, resulting in hypermethylation of the Foxp3 locus, thereby inhibiting Treg differentiation. Changes in miR223 were also associated with lower Treg levels.

(3) PAHs lead to increased expression of Th2-related markers and elevated levels of secreted IL-4 and IL-13. PAHs induce oxidative stress pathways that generate ROS. ROS production may also be caused by increased expression of p40phox, a member of the membrane NADPH oxidase complex.

(4) PM up-regulated the level of CYP 1A1, thereby affecting the activation of human monocytes. CXCL8 production was induced, as was IL-1β secretion by monocytes and activated macrophages.

(5) Exposure to PAHs results in enhanced mast cell signaling, degranulation, mediator and cytokine release, and allergic responses in vivo. Increased expression of several endoplasmic reticulum stress-related markers was also observed.