Visualization of T Cell-Regulated Monocyte Clusters Mediating Keratinocyte Death in Acquired Cutaneous Immunity

Abstract

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.

A Hairy Tale of Monocytes and Contact Hypersensitivity Reactions

“…In aggregate, Liu et al (2018) provide evidence for an antigen recognitiondependent immunological cascade during CHS, in which HFs seem to mediate the encounters and interactions of immune cells that are involved. Several interesting questions that were raised by the study remain to be addressed in future work.…”

“…The work by Liu et al (2018) (OXA)-induced contact hypersensitivity (CHS), they provide evidence for an antigen-recognitionedependent activation of HF keratinocytes that then produce chemokines to recruit monocytes ( Figure 1). The authors began their study by monitoring the spatiotemporal behavior of monocytes during OXAinduced CHS using intravital microscopy.…”

“…Another important aspect of the study that remains to be addressed is whether monocytes directly mediate keratinocyte apoptosis. The observation by Liu et al (2018) that IFNg, a cytokine critical for cytotoxic responses, is only involved in recruiting monocytes is rather counter-intuitive. Accumulation and production of TNFa by monocytes correlated with keratinocyte apoptosis, but direct involvement of monocyte TNF-a remains to be shown.…”

“…Even under physiological conditions, myeloid cells associate with HFs and are thought to mediate destruction of HFs during the hair cycle (Eichmuller et al, 1998). Both OXA challenge as described by Liu et al (2018) and mechanical stress after gentle tape stripping induce CCL2 production (Nagao et al, 2012) that lead to the recruitment of monocytes. Therefore, CCL2 production by HF keratinocytes could be a common response after various insults that involve the epithelium, a response that is then fine-tuned by additional context-dependent factors.…”

Research progress in tissue/organ regional immunity and diseases in China

“…通过学科交叉形成的区域免疫研究的新 技术和新方法及其应用 [36,37] . 利用荧光成像技术还成功展现了皮肤中T细胞 通过调控单核细胞聚集介导皮肤损伤的过程和细胞分 子机制 [38] . 应性CD4 T细胞的重要作用 [42] .…”