Butyrate inhibits Staphylococcus aureus-aggravated dermal IL-33 expression and skin inflammation through histone deacetylase inhibition

Frontiers in Immunology

Immunology

Alan Chuan-Ying Lai¹  Ya-Jen Chang²  Chia-Hui Luo³ 

[1] Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;Department of Pharmaceutical Sciences, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan;Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;Institute of Translational Medicine and New Drug Development, China Medical University, Taichung, Taiwan;Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan;

关键词: atopic dermatitis;    butyrate;    histone deacetylase;    interleukin 33;    keratinocytes;    S. aureus;    S. epidermidis;   

DOI  :  10.3389/fimmu.2023.1114699

 received in 2022-12-02, accepted in 2023-04-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

Atopic dermatitis (AD) is an inflammatory skin disease caused by the disruption of skin barrier, and is dominated by the type 2 immune responses. Patients with AD have a high risk of developing Staphylococcus aureus infection. Interleukin-33 (IL-33), an alarmin, has been implicated in the pathophysiology of AD development. Butyrate, a short chain fatty acid known to be produced from the fermentation of glycerol by the commensal skin bacterium, Staphylococcus epidermidis, has been reported to possess antimicrobial and anti-inflammatory properties that suppress inflammatory dermatoses. However, little is known about the effects of butyrate on dermal IL-33 expression and associated immune response in S. aureus-aggravated skin inflammation in the context of AD. To decipher the underlying mechanism, we established an AD-like mouse model with epidermal barrier disruption by delipidizing the dorsal skin to induce AD-like pathophysiology, followed by the epicutaneous application of S. aureus and butyrate. We discovered that S. aureus infection exacerbated IL-33 release from keratinocytes and aggravated dermal leukocyte infiltration and IL-13 expression. Moreover, we showed that butyrate could attenuate S. aureus-aggravated skin inflammation with decreased IL-33, IL-13, and leukocyte infiltration in the skin. Mechanistically, we demonstrated that butyrate suppressed IL-33 expression and ameliorated skin inflammation through histone deacetylase 3 (HDAC3) inhibition. Overall, our findings revealed the potential positive effect of butyrate in controlling inflammatory skin conditions in AD aggravated by S. aureus infection.

【 授权许可】

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