Background
Atopic dermatitis (AD) is a common disease, with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in the lack of specific treatments. AD is currently considered a biphasic disease, with Th2 predominating acute disease, and a switch to Th1 characterizing chronic disease. Elucidation of the molecular factors that participate in the onset of new lesions and maintenance of chronic disease is critical for the development of targeted therapeutics.
Objectives
We sought to characterize the mechanisms underlying onset and maintenance of AD.
Methods
We investigated intrapersonal sets of transcriptomes from non-lesional, acute and chronic lesions of ten AD patients through genomic, molecular and cellular profiling.
Results
Our study associated the onset of acute lesions with a striking increase in a subset of terminal differentiation proteins, specifically the cytokine-modulated S100A7, S100A8, and S100A9. Acute disease was also associated with significant increases in gene expression levels of major Th22- and Th2- cytokines, and smaller increases in IL-17. A lesser induction of Th1-associated genes was detected in acute disease, although some were significantly up-regulated in chronic disease. Further significant intensification of major Th22 and Th2 cytokines was observed between acute and chronic lesions.
Conclusions
Our data identified increased S100A7, S100A8 and S100A9 gene expression with AD initiation, and concomitant activation of Th2 and Th22 cytokines. Our findings support a model of progressive activation of Th2 and Th22 immune axes from acute to chronic phases, expanding the prevailing view of pathogenesis, with important therapeutic implications.