IL-31 and IL-31 receptor expression in acute experimental canine atopic dermatitis skin lesions.

Abstract

BACKGROUND: To optimise the interleukin (IL)-31-blocking therapy in atopic dermatitis (AD), an understanding of the chronology in the expression of IL-31 and its receptor (IL-31RA) is needed. HYPOTHESIS/OBJECTIVES: (i) To assess the chronological expression of IL-31 in canine AD skin lesions, (ii) to compare it with serum IL-31 levels and macroscopic skin lesion scores, and (iii) to determine the identity of IL-31- and IL-31RA-positive cells. ANIMALS: Four atopic dogs sensitised to house dust mites. METHODS AND MATERIALS: Skin and blood samples were obtained 0 h, 24 h, 48 and 96 h after allergen provocation. IL-31 and IL-31RA single-staining immunofluorescence (IF), as well as IL-31/CD3, IL-31/CD4 and IL-31RA/β3-tubulin double-staining IF were performed. The IL-31-positive cells were counted subjectively. RESULTS: The peak IL-31 expression for three of four dogs occurred 24 h or 48 h postchallenge; it started to decrease at 96 h. There was no significant correlation between the IL-31 expression scores and the serum IL-31 concentrations or the macroscopic skin lesion scores (P = 0.35 and P = 0.36, respectively). The majority of IL-31-positive cells were positive for CD3 (range 91-100%) and CD4 (range 63-100%), indicating that they were helper T (Th) cells. Unexpectedly, sebaceous glands were strongly immunolabelled with IL-31; the extinction of this positivity after immunoabsorption with IL-31 further supported the validity of this immunostaining. The IL-31RA was visualised on keratinocytes and a small proportion of dermal nerves. CONCLUSIONS AND CLINICAL IMPORTANCE: The early and transient production of IL-31 by Th cells supports the concept of using IL-31 inhibiting strategies as a proactive therapy to prevent flares of AD skin lesions.