Pregnane X receptor reduces particulate matter-induced type 17 inflammation in atopic dermatitis

• Published in: Frontiers in immunology Vol. 15; p. 1415350
• Main Authors: Lee, Ji Su, Lee, Youngae, Jang, Sunhyae, Oh, Jang-Hee, Lee, Dong Hun, Cho, Soyun
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2024
• Subjects: air pollution; Animals; atopic dermatitis; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cytokines - metabolism; Dermatitis, Atopic - chemically induced; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - immunology; Dermatitis, Atopic - metabolism; Disease Models, Animal; Female; HaCaT Cells; Humans; Inflammation - immunology; Inflammation - metabolism; Keratinocytes - drug effects; Keratinocytes - immunology; Keratinocytes - metabolism; Male; Mice; Mice, Inbred BALB C; NF-kappa B - metabolism; particulate matter; Particulate Matter - adverse effects; pregnane X receptor; Pregnane X Receptor - genetics; Pregnane X Receptor - metabolism; Signal Transduction - drug effects; Th17 Cells - drug effects; Th17 Cells - immunology; Th17 Cells - metabolism; type 17 inflammation; particulate matter; atopic dermatitis; type 17 inflammation; air pollution; pregnane X receptor
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1415350

Epidemiological evidence suggests that particulate matter (PM) exposure can trigger or worsen atopic dermatitis (AD); however, the underlying mechanisms remain unclear. Recently, pregnane X receptor (PXR), a xenobiotic receptor, was reported to be related to skin inflammation in AD. This study aimed to explore the effects of PM on AD and investigate the role of PXR in PM-exposed AD. and AD-like models were employed, using BALB/c mice, immortalized human keratinocytes (HaCaT), and mouse CD4 T cells. Topical application of PM significantly increased dermatitis score and skin thickness in AD-like mice. PM treatment increased the mRNA and protein levels of type 17 inflammatory mediators, including interleukin (IL)-17A, IL-23A, IL-1β, and IL-6, in AD-like mice and human keratinocytes. PM also activated PXR signaling, and PXR knockdown exacerbated PM-induced type 17 inflammation in human keratinocytes and mouse CD4 T cells. In contrast, PXR activation by rifampicin (a human PXR agonist) reduced PM-induced type 17 inflammation. Mechanistically, PXR activation led to a pronounced inhibition of the nuclear factor kappa B (NF-κB) pathway. In summary, PM exposure induces type 17 inflammation and PXR activation in AD. PXR activation reduces PM-induced type 17 inflammation by suppressing the NF-κB signaling pathway. Thus, PXR represents a promising therapeutic target for controlling the PM-induced AD aggravation.