Succinate and mitochondrial DNA trigger atopic march from atopic dermatitis to intestinal inflammation - 05/04/23
Abstract |
Background |
Atopic march has long been recognized as the progression from atopic dermatitis (AD) to food allergy and asthma during infancy and childhood. However, effective blocking is hampered by the lack of specific biomarkers.
Objectives |
We aimed to investigate the pathologic progression of atopic march trajectories from skin to gut.
Methods |
We built an atopic march mouse model by mechanical skin injury and percutaneous sensitization to peanut allergen. Anaphylaxis from the skin to the small intestine was then investigated by ELISA, RNA sequencing, quantitative real-time PCR, histopathologic analysis, and flow cytometry. The findings from the mice results were also verified by the serum samples of allergic pediatric patients.
Results |
After modeling, inflammation in the skin and small intestine manifested as a mixed type of TH2 and TH17. Further analysis identified elevated succinate in the circulation and expanded tuft cells with upregulated IL-25 in the small intestine, resulting in increased intestinal type 2 innate lymphoid cells and an enhanced type 2 inflammatory response. In addition, free mitochondrial DNA (mtDNA) released after tissue damage was also involved in inflammation march from injured skin to small intestine through the STING pathway. Analysis of clinical samples verified that serum concentrations of succinate and mtDNA were higher in AD allergic children than non-AD allergic children.
Conclusions |
Succinate and mtDNA play key roles in skin-to-gut cross talk during the atopic march from AD to food allergy, and can be considered as biomarkers for risk assessment or targets for atopic march prevention strategies.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Atopic march, succinate, tuft cell, mitochondrial DNA, STING
Abbreviations used : AD, DC, FA, H&E, HRP, ILC, MCPT-1, Mech, MLN, mtDNA, PN, PP, qPCR, rRNA, TSLP, WT
Plan
| The first 2 authors contributed equally to this article, and both should be considered first author. |
|
| Funded by the National Natural Science Foundation of China (grant 81871266), Scientific and Technological Projects of Guangzhou (201804020042), and the National Natural Science Foundation of China (82171764). |
|
| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 151 - N° 4
P. 1050 - avril 2023 Retour au numéro
Article précédent
- Insights into the pathogenesis of hereditary angioedema using genetic sequencing and recombinant protein expression analyses
- Zhen Ren, Shuangxia Zhao, Tiandao Li, H. James Wedner, John P. Atkinson
- ELOVL6 deficiency aggravates allergic airway inflammation through the ceramide-S1P pathway in mice
- Kazufumi Yoshida, Yuko Morishima, Satoshi Ano, Hirofumi Sakurai, Kenya Kuramoto, Yoshiya Tsunoda, Kai Yazaki, Masayuki Nakajima, Mingma Thering Sherpa, Masashi Matsuyama, Takumi Kiwamoto, Yosuke Matsuno, Yukio Ishii, Akio Hayashi, Takashi Matsuzaka, Hitoshi Shimano, Nobuyuki Hizawa
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?