Updated insights into the molecular pathogenesis of canine atopic dermatitis.

Abstract

Atopic dermatitis (AD) is a common and chronic inflammatory skin disease with frequent relapses. The genomics revolution has greatly contributed and revolutionised our knowledge of human AD; understanding the molecular skin fingerprint of AD and associated pathogenic immune pathways has led to preclinical assessments of several novel treatments. Initial studies using microarray analysis to analyse transcriptome (gene expression) changes provided relevant insight on the inflammatory and structural changes occurring at the time of acute or chronic AD skin lesions, or after immunomodulating treatments with drugs ciclosporin and dupilumab, a monoclonal antibody anti-IL4 receptor. The studies revealed that human AD is characterised by the activation of multiple cytokine pathways (predominance of T helper cell [Th]2 with some activation of Th1, Th17 and Th22) as well as dysregulated expression of barrier components in the skin. There are several reports on the expression of different single molecular targets (e.g. interleukin [IL]-13, CCL17 and periostin) in spontaneous canine AD (cAD). However, significant studies of the transcriptome have been limited to a single microarray study analysing chronic AD skin lesions in dogs. While revealing a large number of genes differentially expressed in cAD skin, the small sample size (n = 13 dogs) and the lack of changes in key epidermal barrier and inflammatory cytokine genes in the microarrays have inhibited discussion towards specific immunological changes. This review summarises the current literature regarding the molecular mechanisms of spontaneous cAD, including the recent data regarding RNA sequencing, and compares some pathogenic aspects to the previously published data from human AD.