1. Use of a Canine Model of Atopic Dermatitis to Investigate the Efficacy of a CCR4 Antagonist in Allergen-Induced Skin Inflammation in a Randomized Study 
Clare Murray, Kim Ahrens, Matt Devalaraja, Mike Dymond, Malbinder Fagura, Adam Hargreaves, Alison Holt, Ian Peers, Sally Price, Jaimini Reens, Rob Riley, Rosanna Marsella 
Journal of Investigative Dermatology 
Volume 136, Issue 3, Pages (March 2016)
DOI: /j.jid
Copyright © 2015 The Authors Terms and Conditions

2. Figure 1
Assessment of CADESI score in dogs treated with vehicle, prednisolone, and AZ445. (a) Graphic representation of method used to calculate adjusted area under the curve (AUC) Canine Atopic Dermatitis Extent and Severity Index (CADESI) scores, where adjusted AUC is the total area under the curve minus the area under the red rectangle (background AUC). (b) Adjusted AUC CADESI scores for all animals treated with vehicle, prednisolone, or low- or high-dose AZ445. Each line represents a separate animal, and responders to both doses of CCR4 antagonist are denoted with solid lines. (c) Group mean and standard error for adjusted AUC CADESI for each treatment group. (d) Representative adjusted AUC CADESI data for one of five dogs showing partial response to AZ445 treatment.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
Copyright © 2015 The Authors Terms and Conditions

3. Figure 2
Hematoxylin and eosin–stained skin samples harvested and processed from the lesion periphery (animal 5). (a) Vehicle. Note the extensive and mixed dermal inflammatory cell infiltrate (chronic-active dermatitis; indicated with stars), which forms a predominantly perivascular distribution. Overlying epithelium is thickened and thrown up into folds with diffuse hyperplasia (proliferation) and focal areas of excoriation (thin arrow). Several keratinocytes also display intracellular edema (thick arrow). (b) Low-dose AZ445. Note the reduction in dermal inflammatory cell infiltration (star) and presence of epidermal hyperplasia with pigmentation (thin arrow). (c) High-dose AZ445. In this sample, there is a similar severity of dermal inflammatory cell infiltration (star) and epithelial hyperplasia (thin arrow) compared to b. Superficial dermal blood vessel plexuses show reactive (hypertrophic) endothelium (adjacent to the area of inflammation). (d) Prednisolone. Note the scattered dermal inflammatory cell infiltrates (star) and epithelial morphology (thin arrow), which both are within the range seen in the baseline sample. Bar = 0.5 mm.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
Copyright © 2015 The Authors Terms and Conditions

4. Figure 3
CCR4 IHC/hematoxylin counterstained samples harvested and processed from the lesion periphery (animal 5). (a) Vehicle. Note both the diffusely distributed and the focally aggregated (indicated with stars) CCR4+ inflammatory cell infiltrates within the superficial to deep dermis. (b, c) Low- and high-dose AZ445, respectively. Note both the focally aggregated (stars) and the individual (thin arrows) CCR4+ inflammatory cell infiltrates within the superficial dermis. Although the dermal “hotspot” is more extensive in b, assessment of the entire specimen from b and c was such that they were both graded as “slight” (see Supplementary Table S1). (d) Prednisolone. Note the rare and individual CCR4+ inflammatory cells, predominantly located within the superficial dermis. The quantity and distribution of these cells were within the ranges seen in the baseline sample. Thin arrow denotes CCR4+ cells. IHC, immunohistochemistry. Bar = 0.5 mm.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
Copyright © 2015 The Authors Terms and Conditions

5. Figure 4
Heat map of individual animal histopathology scores for epithelial hyperplasia and dermatitis and IHC scores for CCR4+ cells. Each row represents a separate animal, and each column represents a separate measured score and treatment group. Scores range from 0 to 4, with missing values indicated by white space. IHC, immunohistochemistry.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
Copyright © 2015 The Authors Terms and Conditions

6. Figure 5
Experimental design. Cross-over study design with animals treated daily with test compound or vehicle for 9 consecutive days and HDM allergen challenge after compound dosing on days 3 to 5. HDM, house dust mites.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
Copyright © 2015 The Authors Terms and Conditions