Gene transcription abnormalities in canine atopic dermatitis and related human eosinophilic allergic diseases

Abstract

Canine atopic dermatitis (AD) is clinically similar to human AD, implicating it as a useful model of human eosinophilic allergic disease. To identify cutaneous gene transcription changes in relatively early inflammation of canine AD, microarrays were used to monitor transcription in normal skin (n = 13) and in acute lesional AD (ALAD) and nearby visibly nonlesional AD (NLAD) skin (n = 13) from dogs. Scanning the putative abnormally transcribed genes, several potentially relevant genes, some abnormally transcribed in both NLAD and ALAD (e.g. IL6, NFAM1, MSRA, and SYK), were observed. Comparison for abnormally transcribed genes common to two related human diseases, human AD and asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP), further identified genes or gene sets likely relevant to eosinophilic allergic inflammation. These included: (1) genes associated with alternatively activated monocyte-derived cells, including members of the monocyte chemotactic protein (MCP) gene cluster, (2) members of the IL1 family gene cluster, (3) eosinophil-associated seven transmembrane receptor EMR1 and EMR3 genes, (4) interferon-inducible genes, and (5) keratin genes associated with hair and nail formation. Overall, numerous abnormally transcribed genes were observed only in canine AD; however, many others are common to related human eosinophilic allergic diseases and represent therapeutic targets testable in dogs with AD.

Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions

“…In fact, CCL17 was the highest-expressed gene in microarray and PCR assays at the 48-hour time point. This strong up-regulation of CCL17 has been previously reported in lesional human (Choy et al, 2012;Gittler et al, 2012) and canine AD skin (Maeda et al, 2002;Maeda et al, 2005;Plager et al, 2012), as well as after HDM challenges in sensitized dogs (Marsella et al, 2006).…”

“…In this dog model, HDM induced the up-regulation of genes coding for three mast cell proteases that could be involved in itch induction: chymase, tryptase, and the tryptase-like mastin; the latter being analogous to mouse mast cell protease-11 (Prss34) (note that their human homolog is only a pseudogene). Mastin has been shown previously to be up-regulated in acute canine AD skin (Plager et al, 2012), but its itch-inducing effect has not been studied in animal species in which this protein exists. Chymase has been shown to be a pruritogen in a single old publication (Hagermark et al, 1972).…”

“…Although cathepsin S was not detected in the lesional epidermis of NC/Nga mice with AD (Schonefuss et al, 2010), transgenic mice overexpressing this protein spontaneously develop a chronic AD-like dermatosis (Kim et al, 2012). The expression of CTSS was previously found to be significantly higher in lesional than nonlesional canine AD skin (Plager et al, 2012). Altogether, cathepsin S might be relevant for the induction of atopic skin inflammation and/or its associated itch; the demonstration of its importance awaits trials with interventions specifically targeting this protease.…”

“…Several studies recently reported microarray-based transcriptome profiles obtained from biopsies of visibly lesional or nonlesional human (Esaki et al, 2015;Gittler et al, 2012;Gittler et al, 2013;Saaf et al, 2008;Suarez-Farinas et al, 2011;Suarez-Farinas et al, 2013a) and canine AD skin (Plager et al, 2012;Wood et al, 2009). These studies have provided relevant insights into the inflammatory and structural changes occurring at the time of acute or chronic AD skin lesions or after immunomodulating treatment with cyclosporine (Rozenblit et al, 2014), narrow-band UVB (Suarez-Farinas et al, 2013b), or the monoclonal antibody dupilumab (Hamilton et al, 2014).…”

A review of the roles of keratinocyte‐derived cytokines and chemokines in the pathogenesis of atopic dermatitis in humans and dogs

“…136 A microarray analysis in acute cAD skin lesions revealed that the transcription of il-33 was approximately three times higher than that in healthy dogs. 142 Transcription analyses by microarray and RT-qPCR demonstrated the increased transcription of il-33 in the skin of dogs sensitized to HDM allergens. 122 These results suggest that canine IL-33 is likely involved in the pathogenesis of cAD, similar to human AD.…”