Chiocchetti Roberto, Salamanca Giulia, De Silva Margherita, Gobbo Francesca, Aspidi Francesca, Cunha Rodrigo Zamith, Galiazzo Giorgia, Tagliavia Claudio, Sarli Giuseppe, Morini Maria
Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
Faculty of Veterinary Medicine, Università degli Studi di Teramo, Località Piano D'Accio, Teramo, Italy.
Front Vet Sci. 2022 Sep 15;9:987132. doi: 10.3389/fvets.2022.987132. eCollection 2022.
Atopic dermatitis (AD) is one of the most common cutaneous inflammatory and pruritic diseases in dogs. Considering its multifactorial nature, AD can be a challenging disease to manage, and the therapeutic strategy must often be multimodal. In recent years, research has been moving toward the use of natural products which have beneficial effects on inflammation and itching, and no side effects. Cannabinoid receptors have been demonstrated to be expressed in healthy and diseased skin; therefore, one of the potential alternative therapeutic targets for investigating AD is the endocannabinoid system (ECS).
To immunohistochemically investigate the expression of the cannabinoid receptor type 2 (CB2R), and the cannabinoid-related receptors G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) in mast cells (MCs), macrophages, dendritic cells (DCs), T cells, and neutrophils of the skin of dogs with AD.
Samples of skin tissues were collected from eight dogs with AD (AD-dogs).
The immunofluorescent stained cryosections of the skins of 8 dogs with AD having antibodies against CB2R, GPR55, TRPV1, TRPA1 were semiquantitatively evaluated. The inflammatory cells were identified using antibodies against tryptase (mast cells), ionized calcium binding adaptor molecule 1 (IBA1) (macrophages/DCs), CD3 (T cells), and calprotectin (neutrophils). The proportions of MCs, macrophages/DCs, cells, and neutrophils expressing CB2R, GPR55, TRPV1 and TRPA1 were evaluated.
The cells of the inflammatory infiltrate showed immunoreactivity (IR) for all or for some of the cannabinoid and cannabinoid-related receptors studied. In particular, MCs and macrophages/DCs showed CB2R-, GPR55-, TRPA1-, and TRPV1-IR; T cells showed CB2R-, GPR55- and TRPA1-IR, and neutrophils expressed GPR55-IR. Co-localization studies indicated that CB2R-IR was co-expressed with TRPV1-, TRPA1-, and GPR55-IR in different cellular elements of the dermis of the AD-dogs.
Cannabinoid receptor 2, and cannabinoid-related receptors GPR55, TRPV1 and TRPA1 were widely expressed in the inflammatory infiltrate of the AD-dogs. Based on the present findings, the ECS could be considered to be a potential therapeutic target for dogs with AD, and may mitigate itch and inflammation.
特应性皮炎（AD）是犬类最常见的皮肤炎症性瘙痒疾病之一。鉴于其多因素性质，AD的治疗颇具挑战性，治疗策略通常必须是多模式的。近年来，研究已转向使用对炎症和瘙痒有有益作用且无副作用的天然产物。已证明大麻素受体在健康和患病皮肤中均有表达；因此，研究AD的潜在替代治疗靶点之一是内源性大麻素系统（ECS）。
通过免疫组织化学方法研究2型大麻素受体（CB2R）、大麻素相关受体G蛋白偶联受体55（GPR55）、瞬时受体电位香草酸亚型1（TRPV1）和锚蛋白1（TRPA1）在AD犬皮肤的肥大细胞（MCs）、巨噬细胞、树突状细胞（DCs）、T细胞和中性粒细胞中的表达。
从8只AD犬（AD犬）收集皮肤组织样本。
对8只AD犬皮肤的免疫荧光染色冰冻切片进行半定量评估，这些切片使用了抗CB2R、GPR55、TRPV1、TRPA1的抗体。使用抗类胰蛋白酶（肥大细胞）、离子钙结合衔接分子1（IBA1）（巨噬细胞/DCs）、CD3（T细胞）和钙卫蛋白（中性粒细胞）的抗体鉴定炎症细胞。评估表达CB2R、GPR55、TRPV1和TRPA1的MCs、巨噬细胞/DCs、T细胞和中性粒细胞的比例。
炎症浸润细胞对所研究的全部或部分大麻素及大麻素相关受体显示免疫反应性（IR）。特别是，MCs和巨噬细胞/DCs显示CB2R、GPR55、TRPA1和TRPV1-IR；T细胞显示CB2R、GPR55和TRPA1-IR，中性粒细胞表达GPR55-IR。共定位研究表明，在AD犬真皮的不同细胞成分中，CB2R-IR与TRPV1-IR、TRPA1-IR和GPR55-IR共表达。
大麻素受体2以及大麻素相关受体GPR55、TRPV1和TRPA1在AD犬的炎症浸润中广泛表达。基于目前的研究结果，ECS可被认为是AD犬的潜在治疗靶点，可能减轻瘙痒和炎症。
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