2. Academic Validation
  3. NLRX1 deficiency exacerbates skin inflammation in atopic dermatitis by disrupting mitophagy

NLRX1 deficiency exacerbates skin inflammation in atopic dermatitis by disrupting mitophagy

  • Clin Immunol. 2025 Mar:272:110442. doi: 10.1016/j.clim.2025.110442.
Lixin Yue 1,  Pei Qiao 1,  Xia Li 1,  Ke Xue 1,  Bingyu Pang 1,  Yaxing Bai 1,  Pu Song 1,  Huanhuan Qu 1,  Hongjiang Qiao 1,  Danni Sun 2,  Xingan Wu 2,  Rongrong Liu 3,  Gang Wang 4,  Erle Dang 5
Affiliations

Affiliations

  • 1 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
  • 2 Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
  • 3 Department of Microbiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: rong4713@163.com.
  • 4 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: xjwgang@fmmu.edu.cn.
  • 5 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: dangerle@fmmu.edu.cn.
PMID: 39884322 DOI: 10.1016/j.clim.2025.110442
Abstract

NLRX1 is an important regulator of inflammatory signaling in innate immune cells. Recent studies indicate NLRX1 activation may be a novel mechanism for inflammatory diseases, however, it has not been explored in atopic dermatitis (AD). Our study aims to investigate the potential role of NLRX1 in the pathogenesis of AD. We observed a significant decrease in NLRX1 expression in AD skin lesions and MC903-indued AD dermatitis. NLRX1 deficiency exacerbated AD inflammation, characterized by increased skin thickness, exacerbated inflammatory infiltration, and compromised skin barrier function. Mechanistically, NLRX1 regulated TSLP expression through Parkin-PINK1-mediated Mitophagy in keratinocytes. Furthermore, topical application of NLRX1 agonist alleviated AD progression, including reduced ear thickness, diminished redness, and improved skin barrier function. This study provides novel insights into the regulatory role of NLRX1 in skin inflammation in AD, highlighting the potential therapeutic implications of targeting NLRX1 and Mitophagy in AD treatment.

Keywords

Atopic dermatitis; Inflammation; Keratinocytes; Mitophagy; NLRX1; Skin.

Figures
Products