Succinate and mitochondrial DNA trigger atopic march from atopic dermatitis to intestinal inflammation.
J Allergy Clin Immunol
; 151(4): 1050-1066.e7, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-36587852
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Dermatitis Atópica
/
Hipersensibilidad a los Alimentos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2023
Tipo del documento:
Article
País de afiliación:
China