PSIX-7 - Attenuation of immune allergic response pathways in canines with dermatological problems fed a polyphenol-rich food

Abstract: Pathogenesis of canine dermatological problems is mediated by multiple effector cells including lymphocytes, eosinophils, and mast cells. We have previously reported a significant increase in the gene expression of interleukin-5 receptor alpha (IL-5RA) in derm dogs when compared to controls, as well as a modest increase in C-C chemokine receptor 3 (CCR3), IL-4 and IL-5. We now investigated whether 2 tests foods (one rich in polyphenols) would provide beneficial effects in canines with dermatological problems (n=8) when compared to controls (n=8). Dogs were pre-fed control food for 28 days and then divided into two groups based on their age, gender and phenotype (Healthy, Derm) followed by a cross-over design. At each phase, dogs were fed for 42 days with test food 1 (TF1) and the second group was fed with a higher polyphenol content Test food 2 (TF2) for 42 days followed by a crossover. Blood samples were collected at end of pre-feed, end of phase 1, and end of phase 2. Study was approved by IACUC and AWC, Hill’s PNC. RNA was extracted from blood collected in PAXgene tubes and gene expression was investigated using the NanoString nCounter® platform. To assess the food effect, a mixed model analysis was performed using treatment (food) as a fixed effect and animal as random effect using JMPPro. TF2 fed dogs decreased pruritus scores, increased the response rate (improvement %) to 30.77% when compared to dogs fed TF1. There was a significant decrease in the interleukin-5 receptor alpha (IL-5RA) in dogs fed TF2 when compared to baseline (p < 0.05). IL-5RA is a receptor expressed on eosinophils as well as committed eosinophil precursors in the bone marrow. There was also a decrease in FCRL2 in dogs fed TF2 (p < 0.05). This gene is preferentially expressed in memory B-cells and plasma cells and also involved in B-cell receptor signaling. The generation of plasma cells requires naïve B cell activation to differentiate into antibody secreting cells or memory B cells. Given the lower levels of FCRL2 with TF2, it is possible that the production of subsequent IgE is attenuated. Another signaling molecule that was significantly decreased with TF2 was the innate immune response molecule C3AR1, a receptor for Complement C3a that induces chemotaxis, granule release, as well as superoxide production. TF1 and TF2 significantly decreased CCR3, a receptor on eosinophils and basophils. CCR3 antagonists are effective in reducing allergic inflammation. Our results indicate the important role of eosinophilic allergic response in dermatological disorders in dogs. TF2 appears to have a beneficial effect in attenuating allergy-inducing signaling pathways of innate and adaptive immune responses. Targeting these molecules may be important as part of newer therapeutic approaches, including nutritional strategies, to manage dermatological problems in dogs.