Mast cell communication and collaboration with macrophages – impact on severity, course and resolution of inflammation

肥大细胞与巨噬细胞的通讯和协作 â 对炎症严重程度、病程和消退的影响

• 批准号: 456679927
• 负责人: Professorin Dr. Anne Dudeck
• 金额: --
• 依托单位: Institut für Molekulare und Klinische Immunologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/456679927?language=en
• 关键词: Mast; cell; communication; collaboration; macrophages

Mast cells (MC) and macrophages (Mph) are both tissue resident sentinel cells equipped with a plethora of sensing receptors but distinct effector functions, and reside in close proximity in peripheral tissues such as the skin. Using intravital 2-photon microscopy of transgenic MC/Mph double reporter mice, we recently detected an alternate positioning and physical interaction between MCs and Mphs at dermal blood vessels. Additionally, Mphs engulf intact MC granules exocytosed by MC degranulation upon skin inflammation. Our findings let us hypothesize that MCs and Mph dynamically communicate in healthy and inflammatory conditions and may collaborate in the recruitment of additional effector immune cells upon skin inflammation. This interaction may impact on Mph plasticity and function in the acute phase but also in the resolution of skin inflammation. Importantly, MCs may modulate Mph polarization and functionality by three modes of action: release of soluble mediators; physical contact and dynamic interaction; and sensing and uptake of intact MC granules. In this proposal, we aim to determine the spatiotemporal distribution of MC/Mph communication in the skin under physiologic and inflammatory conditions. Furthermore, we will investigate how MCs modulate Mph plasticity and functions in innate and adaptive immune responses upon contact hypersensitivity and in the resolution of inflammation. Finally we aim to detail mechanisms of MC effects on Mph polarization and function depending on the different modes of communication.

肥大细胞（MC）和巨噬细胞（Mph）都是组织驻留的哨兵细胞，其配备有过多的传感受体但具有不同的效应器功能，并且紧密邻近地驻留在外周组织如皮肤中。使用转基因MC/Mph双报告小鼠的活体2-光子显微镜，我们最近检测到一个替代定位和皮肤血管的MCs和Mphs之间的物理相互作用。 此外，Mphs吞噬皮肤炎症时MC脱粒而胞吐的完整MC颗粒。我们的研究结果让我们假设MC和Mph在健康和炎症条件下动态通信，并可能在皮肤炎症时招募额外的效应免疫细胞。这种相互作用可能会影响急性期Mph的可塑性和功能，也可能影响皮肤炎症的消退。重要的是，MC可以通过三种作用模式调节Mph极化和功能：释放可溶性介质;物理接触和动态相互作用;以及完整MC颗粒的感测和摄取。在这个建议中，我们的目标是确定在生理和炎症条件下的MC/Mph通信在皮肤中的时空分布。此外，我们将探讨如何MC调节Mph可塑性和功能的先天性和适应性免疫反应后，接触性超敏反应和炎症的决议。最后，我们的目标是详细的机制MC影响Mph极化和功能取决于不同的通信模式。