T cells in dog skin with atopic dermatitis make allergy-related

Abstract

BACKGROUND: T Cells play a major role in the immunopathogenesis of canine atopic dermatitis (cAD). However, the significance of cutaneous regulatory T cells (Tregs) and CD8(+) T cells is currently unclear. HYPOTHESIS/OBJECTIVES: The study aimed to evaluate the presence and distribution of Tregs in cAD and healthy skin and to determine the cytokine production of cutaneous CD4(+) and CD8(+) T cells. ANIMALS: Biopsies were taken from four dogs with cAD (lesional and nonlesional skin) and four healthy control dogs. METHODS: Distribution patterns of T-cell subtypes in cAD lesional, nonlesional and control skin were evaluated by immunohistochemistry. Phenotypic characterization of T cells from skin explant cultures and enzymatic digestions was performed using flow cytometry. Cytokine production of sorted CD4(+) and CD8(+) explant-derived T cells was measured by RT-qPCR. RESULTS: Regulatory T cells phenotypically characterized by CD25(+) FoxP3(+) were found in both CD4(+) and CD8(+) subsets of skin explant and digestion samples. The percentages of CD4(+) CD25(+) cells that were FoxP3(+) were similar in cAD and control skin. In atopic lesional and nonlesional explant samples, lower FoxP3(+) percentages of CD8(+) CD25(+) cells were seen compared with control skin. The presence of predominantly periadnexal CD25(+) FoxP3(+) cells was confirmed by immunohistochemistry in lesional, nonlesional and control skin. The CD4(+) /CD8(+) ratio was less than one in cAD skin with both skin explant and digestion methods. CD4(+) and CD8(+) T-cell subsets of lesional and nonlesional cAD skin were capable of producing interleukin-13, interleukin-22 and interferon-γ. CONCLUSIONS AND CLINICAL IMPORTANCE: Both CD4(+) and CD8(+) T cells are likely to contribute to the immunopathogenesis of cAD through the production of interleukin-13, interleukin-22 and interferon-γ. In both subsets, functional analysis of FoxP3(+) cells is essential to determine their role.