Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, Koserstraße. 20, Berlin, 14195, Germany.
Institute of Animal Pathology, Department of Veterinary Medicine, Freie Universität Berlin, Robert-von- Ostertag-Straße 15, Berlin, 14163, Germany.
BMC Immunol. 2024 Feb 12;25(1):17. doi: 10.1186/s12865-024-00604-4.
Itch sensitization has been reported in patients with chronic allergic skin diseases and observed in a mouse model of allergic contact dermatitis (ACD). There is evidence suggesting that neuroimmune interactions may contribute to itch sensitization, as an increase in dendritic cells (DCs) within ganglia has been observed during allergic conditions. However, how DCs interact with sensory neurons in ganglia during allergic conditions is still not known. This study aims to investigate the role of DCs in dorsal root ganglion (DRG) under ACD conditions, specifically focusing on itch sensitization within the DRG. The tolylene-2,4-diisocyanate (TDI) mouse model for ACD and the co-culture model of DCs and DRG neurons was employed in this study.
We successfully induced ACD by TDI, as evidenced by the development of edema, elevated total serum IgE levels, and an observed itch reaction in TDI-sensitized mice. Calcium imaging and RT-qPCR analysis revealed that TDI-sensitized mice exhibited signs of peripheral sensitization, including a higher percentage of neurons responding to pruritogens and increased activation and expression of itch receptors in excised DRG of TDI-sensitized mice. Immunofluorescence and flow cytometric analysis displayed an increase of MHCII cells, which serves as a marker for DCs, within DRG during ACD. The co-culture study revealed that when DRG neurons were cultured with DCs, there was an increase in the number of neurons responsive to pruritogens and activation of itch receptors such as TRPA1, TRPV1, H1R, and TRPV4. In addition, the immunofluorescence and RT-qPCR study confirmed an upregulation of TRPV4.
Our findings indicate that there is an increase of MHCII cells and itch peripheral sensitization in DRG under TDI-induced ACD condition. It has been found that MHCII cells in DRG might contribute to the itch peripheral sensitization by activating itch receptors, as shown through co-culture studies between DRG neurons and DCs. Further studies are required to identify the specific mediator(s) responsible for peripheral sensitization induced by activated DCs.
慢性过敏性皮肤疾病患者会出现瘙痒致敏现象，变应性接触性皮炎（ACD）的小鼠模型中也观察到了这一现象。有证据表明，神经免疫相互作用可能导致瘙痒致敏，因为在过敏状态下，神经节内树突状细胞（DCs）数量增加。然而，在过敏状态下，DCs 如何与神经节中的感觉神经元相互作用仍不清楚。本研究旨在探讨 ACD 条件下背根神经节（DRG）中 DCs 的作用，特别是关注 DRG 中的瘙痒致敏作用。本研究采用甲苯-2,4-二异氰酸酯（TDI）ACD 小鼠模型和 DCs 与 DRG 神经元共培养模型。
我们成功地通过 TDI 诱导 ACD，表现为 TDI 致敏小鼠出现水肿、总血清 IgE 水平升高和瘙痒反应。钙成像和 RT-qPCR 分析显示，TDI 致敏小鼠表现出外周致敏迹象，包括对致痒原反应的神经元比例增加，以及 TDI 致敏小鼠 DRG 中瘙痒受体的激活和表达增加。免疫荧光和流式细胞术分析显示，在 ACD 期间，DRG 中作为 DCs 标志物的 MHCII 细胞增加。共培养研究显示，当 DRG 神经元与 DCs 共培养时，对致痒原反应的神经元数量增加，TRPA1、TRPV1、H1R 和 TRPV4 等瘙痒受体的激活增加。此外，免疫荧光和 RT-qPCR 研究证实 TRPV4 上调。
我们的研究结果表明，在 TDI 诱导的 ACD 条件下，DRG 中 MHCII 细胞增加和瘙痒外周致敏。通过 DRG 神经元与 DCs 共培养研究发现，DRG 中的 MHCII 细胞可能通过激活瘙痒受体导致瘙痒外周致敏。需要进一步的研究来确定激活的 DCs 诱导的外周致敏的具体介质。
