Role of IL‐5/IL‐5RA Axis in Eosinophilic Allergic Response in Canines with Dermatological Problems

Abstract

The inflammatory response in canines with dermatological problems is likely mediated by multiple effector cells including lymphocytes, eosinophils, and mast cells. Several cytokines produced by Th2 lymphocytes including IL‐4 and IL‐31 are implicated in the pathogenesis of dermatological disorders and subsequent elevation of serum IgE and increased inflammation in the skin. Our study assessed the gene expression profile of inflammatory markers in blood samples collected from canines with dermatological problems to identify novel inflammatory markers that could lead to improved nutritional interventions. This study was approved by IACUC and the Animal Welfare Committee, Hills PNC. Gene expression was assessed in blood collected in PAXgene RNA tubes from canines with dermatological problems (Derm; n = 12; 4‐14yr) or controls (Con; n = 16; 4‐14yr), as diagnosed clinically by a veterinarian. Changes in a panel of 84 genes were analyzed using the RT2 ProfilerTM PCR Array for dog inflammatory cytokines and receptors. Blood was also analyzed for complete blood count (CBC) for circulating concentrations of leukocytes. There was a significant increase in the interleukin‐5 receptor alpha (IL‐5RA) level in derm dogs when compared to controls (1.71 fold, p<0.05). There was also an increase in C‐C chemokine receptor 3 (CCR3), IL‐4 and IL‐5 (all >1.25 fold, ns) in the derm dogs. IL‐5RA and CCR3 are receptors that are also expressed on eosinophils and IL‐4 is involved in the production of IL‐5. Given that IL‐5 plays a key role in the maturation and activation of eosinophils, and committed eosinophil precursors in the bone marrow express IL‐5RA and CCR3, our results indicate an important role of the IL‐5/IL‐5RA axis in dermatological disorders in canines. Consistent with this, there was a significant increase in circulating eosinophil levels in derm dogs (n=14; 0.35 x 103/μl) when compared to controls (0.28 x 103/μl; p<0.05). Further, increased levels of IL‐4 and IL‐5 are associated with increased serum IgE and subsequent allergic response. We report increased serum IgE levels in derm dogs (147.7 ± 52.9 µg/ml; n=14) when compared with healthy dogs (72.5 ± 49.5 µg/ml). In addition, other pro‐inflammatory proteins that were increased in derm dogs include CCR10 (1.67), CCL16 (1.34), CCR8 (1.35), CXCR5 (1.34), LTA (1.37), and BMP2 (1.44). Interestingly, derm dogs showed a decreased level of NAMPT, a putative cytokine that is hypothesized to enhance the maturation of B cell precursors (‐1.37 fold decrease). Taken together, our results indicate the important role of eosinophilic allergic response in dermatological disorders in dogs. Targeting the IL‐5/IL‐5RA signaling axis may be important as part of newer therapeutic approaches, including nutritional strategies, to reduce dermatitis in dogs.