Quantitative Changes Accompany Transition from Nonlesional to Acute to Chronic Inflammation in AD

Atopic dermatitis on arm
The sequence of AD progression from acute to chronic stages, with progressively heightened inflammatory response for all major immune axes, has been delineated.

In regard to cytokine network activation, the primary distinction between acute and chronic atopic dermatitis (AD) is more quantitative rather than qualitative in nature, and specific components are associated with the persistence and chronicity of inflammation related to AD, according to study research published in the Journal of Allergy and Clinical Immunology.

The study was an analysis of transcriptome changes found in paired nonlesional skin, acute AD lesions, and chronic AD lesions taken from skin biopsies of 11 patients with moderate to severe AD and 38 healthy controls. These changes were taken via RNA sequencing, and in vivo and histologic assays were conducted to examine the findings.

The majority of changes in acute AD were also present in chronic AD, and the investigators suggested that approximately 74% of genes that were dysregulated in acute lesions persisted or were expressed in chronic AD lesions. Only 34% of genes dysregulated in chronic AD lesions were differentially expressed in lesions at the acute stage.

Genes that participate in skin barrier maintenance and repair, immunoglobulin production, inhibition of CD4+ T-cell activation, and tryptophan metabolism were statistically differentially expressed between chronic and acute lesions. In addition, the investigators found that response genes TNF, TH1, TH2, and TH17 were enriched in nonlesional AD skin. Few changes were observed in acute and nonlesional AD in terms of these set of genes.

Acute AD lesions exhibited noticeable dendritic-cell signatures and significant enrichment in TH1, TH2, and TH17 responses. In addition, acute AD lesions demonstrated increased IL-36 and thymic stromal lymphopoietin expression, and expression of these components were increased in chronic AD lesions. Progressive changes were observed in vasculature and maturation of dendritic-cell subsets with chronicity. Transcription factor FOXK1 was found to act as a negative immune regulator in chronic AD.

The investigators wrote that their “findings provide novel insights into the pathogenesis of AD and highlight previously understudied pathways in AD pathogenesis that may be amenable to future therapeutic targeting.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Tsoi LC, Rodriguez E, Stölzl D, et al. Progression of acute-to-chronic atopic dermatitis is associated with quantitative rather than qualitative changes in cytokine responses. J Allergy Clin Immunol. 2020;145(5):1406-1415.