Maskey Anish R, Mo Xian, Li Xiu-Min
Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, 10595, USA.
The Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, Guangzhou, People's Republic of China.
J Inflamm Res. 2024 Oct 2;17:6955-6970. doi: 10.2147/JIR.S467327. eCollection 2024.
Atopic dermatitis (AD) is a complex immune-mediated abnormality of the skin characterized by impaired barrier function, eczematous dermatitis, chronic pruritus and itch. The immunological response in AD is mediated by a Th2-dominated immune response in the early acute phase followed by a Th1/ Th2 mixed immune response in the chronic phase. AD is the first step of the "atopic march" that progresses into food allergy, allergic rhinitis, and asthma. Different models are indispensable for studying AD pathogenesis and for designing pre-clinical studies for therapeutic discovery. They reflect the characteristic morphological features of typical human AD with regard to epidermal thickening, hyperkeratosis, acanthosis, and spongiosis and help understand the immunopathogenesis of the disease with respect to IgE levels and cellular infiltration of eosinophils, mast cells, and lymphocytes. Although it is difficult to replicate all human AD clinical features in a model, several AD in vivo models comprising spontaneous, induced, transgenic, and humanized and in vitro models, including 2D, co-culture, and 3D, have been described previously. However, several questions remain regarding whether these models satisfactorily reflect the complexity of human AD. Therefore, this review comprehensively highlights the diversity of currently available models and provides insights into the selection of suitable models based on research questions. It also summarizes the diverse mechanisms associated with each model, which may be valuable for better study design to test new therapeutic options.
特应性皮炎（AD）是一种复杂的免疫介导性皮肤异常，其特征为屏障功能受损、湿疹性皮炎、慢性瘙痒。AD的免疫反应在急性期早期由以Th2为主导的免疫反应介导，在慢性期则由Th1/Th2混合免疫反应介导。AD是“特应性进程”的第一步，该进程会发展为食物过敏、过敏性鼻炎和哮喘。不同的模型对于研究AD发病机制以及设计用于治疗发现的临床前研究不可或缺。它们反映了典型人类AD在表皮增厚、角化过度、棘层肥厚和海绵形成方面的特征性形态学特征，并有助于从IgE水平以及嗜酸性粒细胞、肥大细胞和淋巴细胞的细胞浸润方面理解该疾病的免疫发病机制。尽管很难在模型中复制所有人类AD的临床特征，但先前已经描述了几种AD体内模型，包括自发、诱导、转基因和人源化模型，以及体外模型，包括二维、共培养和三维模型。然而，关于这些模型是否能令人满意地反映人类AD的复杂性仍存在一些问题。因此，本综述全面强调了当前可用模型的多样性，并基于研究问题提供了选择合适模型的见解。它还总结了与每个模型相关的多种机制，这对于更好地设计测试新治疗方案的研究可能具有重要价值。
