Department of In Vivo Biology & Safety, LEO Pharma A/S, Ballerup, Denmark
Department of In Vivo Biology & Safety, LEO Pharma A/S, Ballerup, Denmark.
In Vivo. 2021 Jul-Aug;35(4):1985-1997. doi: 10.21873/invivo.12467.
BACKGROUND/AIM: The pathway of initiation of psoriasis comprises the differentiation and infiltration of T-helper 17 (Th17) cells into the skin, characterized by the production of interleukin 17A and 17F (IL-17A/IL-17F) among other cytokines, resulting in a downstream cascade of events. Due to the lack of simplicity in psoriasis models, we aimed to develop an easily and rapidly inducible mouse model for the IL-23/IL-17 pathway with quick readouts from a straightforward lavaging process and with detectable cytokine levels.
We utilized the 6-day air-pouch mouse model, injected with a combination of anti-CD3, IL-23 and IL-1β. At 24, 48 and 72 h, intra-pouch secretion of IL-17A, IL-17F and C-X-C motif chemokine ligand 1 were measured. Skin biopsies were collected and immune cell infiltration evaluated, and intra-pouch immune cells were isolated and analyzed.
The combination of anti-CD3, IL-23 with and without IL-1β significantly increased intra-pouch levels of IL-17A/IL-17F at 24 and 72 h, triggering a downstream production of C-X-C motif chemokine ligand 1. The cytokines were detectable even 72 h post-induction. T-cell receptor beta was down-regulated on CD4 and CD8 T-cells, indicating intra-pouch T-cell activation. Αnti-CD3 induced CD3 cell migration into the subcutis and the lining tissue surrounding the cavity of the air pouch, where in the latter, a similar distribution pattern of Il17a mRNA-expressing cells was also observed. However, no Th17 cell differentiation nor changes in IL-17A granulocytes were observed.
The induced air-pouch mouse model induced with a cocktail of anti-CD3, IL-23 with or without IL-1β is able to mirror the IL-23/IL-17 axis of psoriasis-like inflammation characterized by immune cell infiltration and cytokine secretion.
背景/目的：银屑病的发病途径包括辅助性 T 细胞 17（Th17）细胞向皮肤的分化和浸润，其特征是产生白细胞介素 17A 和 17F（IL-17A/IL-17F）等细胞因子，导致下游级联事件的发生。由于银屑病模型缺乏简单性，我们旨在开发一种简单、快速诱导的小鼠模型，用于 IL-23/IL-17 途径，该模型具有简单冲洗过程的快速读数，并具有可检测的细胞因子水平。
我们利用 6 天的气袋小鼠模型，注射抗 CD3、IL-23 和 IL-1β 的组合。在 24、48 和 72 小时时，测量囊内 IL-17A、IL-17F 和 C-X-C 基序趋化因子配体 1 的分泌。收集皮肤活检并评估免疫细胞浸润，并分离和分析囊内免疫细胞。
抗 CD3、IL-23 与和不与 IL-1β 的组合在 24 和 72 小时显着增加了囊内的 IL-17A/IL-17F 水平，引发了 C-X-C 基序趋化因子配体 1 的下游产生。即使在诱导后 72 小时也可以检测到细胞因子。T 细胞受体 β 在 CD4 和 CD8 T 细胞上下调，表明囊内 T 细胞活化。抗 CD3 诱导 CD3 细胞迁移到皮下组织和气囊腔的衬里组织中，在后一种情况下，也观察到 Il17a mRNA 表达细胞的类似分布模式。然而，没有观察到 Th17 细胞分化或 IL-17A 粒细胞的变化。
用抗 CD3、IL-23 与或不与 IL-1β 的鸡尾酒诱导的气袋小鼠模型能够模拟银屑病样炎症的 IL-23/IL-17 轴，其特征是免疫细胞浸润和细胞因子分泌。
