Supplementary Material for: Polarized Airway Epithelial Models for Immunological Co-Culture Studies

Epithelial cells line all cavities and surfaces throughout the body and play a substantial role in maintaining tissue homeostasis. Asthma and other atopic diseases are increasing worldwide and allergic disorders are hypothesized to be a consequence of a combination of dysregulation of the epithelial response towards environmental antigens and genetic susceptibility, resulting in inflammation and T cell-derived immune responses. In vivo animal models have long been used to study immune homeostasis of the airways but are limited by species restriction and lack of exposure to a natural environment of both potential allergens and microflora. Limitations of these models prompt a need to develop new human cell-based in vitro models. A variety of co-culture systems for modelling the respiratory epithelium exist and are available to the scientific community. The models have become increasingly sophisticated and specific care needs to be taken with regard to cell types, culture medium and culture models, depending on the aim of the study. Although great strides have been made, there is still a need for further optimization, and optimally also for standardization, in order for in vitro co-culture models to become powerful tools in the discovery of key molecules dictating immunity and/or tolerance, and for understanding the complex interplay that takes place between mucosa, airway epithelium and resident or infiltrating immune cells. This review focuses on current knowledge and the advantages and limitations of the different cell types and culture methods used in co-culture models of the human airways.

上皮细胞（Epithelial cells）覆盖于人体所有腔道与表面，在维持组织稳态（tissue homeostasis）中发挥关键作用。哮喘与其他特应性疾病（atopic diseases）在全球范围内发病率持续攀升，学界普遍认为过敏性疾病（allergic disorders）的发生是上皮细胞对环境抗原（environmental antigens）应答失调与遗传易感性（genetic susceptibility）共同作用的结果，最终引发炎症反应与T细胞介导的免疫应答（T cell-derived immune responses）。
长期以来，体内动物模型（in vivo animal models）被用于研究气道免疫稳态（immune homeostasis），但此类模型受限于物种差异，且无法模拟包含潜在过敏原与微生物群（microflora）的自然暴露环境。
上述模型的局限性推动了新型基于人体细胞的体外模型（in vitro models）的研发需求。目前已有多种用于模拟呼吸道上皮（respiratory epithelium）的共培养系统（co-culture systems），并已向科研群体开放使用。
此类模型的复杂度与精细化程度不断提升，因此需根据研究目的，谨慎选择细胞类型、培养基（culture medium）与培养模型。尽管目前已取得长足进展，但体外共培养模型若要成为发掘调控免疫与免疫耐受关键分子、解析黏膜（mucosa）、气道上皮与常驻免疫细胞（resident immune cells）、浸润免疫细胞（infiltrating immune cells）间复杂相互作用的有力工具，仍需进一步优化，理想情况下还应实现标准化。
本综述聚焦当前研究进展，以及人体气道共培养模型中所使用的各类细胞类型与培养方法的优势与局限性。