Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Biomedical Photonics of Ministry of Education, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Invest Dermatol. 2018 Jun;138(6):1328-1337. doi: 10.1016/j.jid.2018.01.018. Epub 2018 Feb 1.
It remains unclear how monocytes are mobilized to amplify inflammatory reactions in T cell-mediated adaptive immunity. Here, we investigate dynamic cellular events in the cascade of inflammatory responses through intravital imaging of a multicolor-labeled murine contact hypersensitivity model. We found that monocytes formed clusters around hair follicles in the contact hypersensitivity model. In this process, effector T cells encountered dendritic cells under regions of monocyte clusters and secreted IFN-γ, which mobilizes CCR2-dependent monocyte interstitial migration and CXCR2-dependent monocyte cluster formation. We showed that hair follicles shaped the inflammatory microenvironment for communication among the monocytes, keratinocytes, and effector T cells. After disrupting the T cell-mobilized monocyte clusters through CXCR2 antagonization, monocyte activation and keratinocyte apoptosis were significantly inhibited. Our study provides a new perspective on effector T cell-regulated monocyte behavior, which amplifies the inflammatory reaction in acquired cutaneous immunity.
单核细胞如何被动员来放大 T 细胞介导的适应性免疫中的炎症反应尚不清楚。在这里，我们通过对多色标记的小鼠接触超敏反应模型的活体成像来研究炎症反应级联中的动态细胞事件。我们发现，单核细胞在接触超敏反应模型中围绕毛囊形成簇。在这个过程中，效应 T 细胞在单核细胞簇区域遇到树突状细胞，并分泌 IFN-γ，这会动员 CCR2 依赖性单核细胞间质迁移和 CXCR2 依赖性单核细胞簇形成。我们表明，毛囊为单核细胞、角质形成细胞和效应 T 细胞之间的通信塑造了炎症微环境。通过 CXCR2 拮抗作用破坏 T 细胞动员的单核细胞簇后，单核细胞的激活和角质形成细胞的凋亡明显受到抑制。我们的研究为效应 T 细胞调节单核细胞行为提供了新的视角，这种行为放大了获得性皮肤免疫中的炎症反应。
