FOR 2599: Tissue type 2 responses: Mechanisms of induction and regulation

FOR 2599：2 型组织反应：诱导和调节机制

• 批准号: 322359157
• 金额: --
• 依托单位: Max-Planck-Institut für Biochemie (MPIB)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/322359157?language=en
• 关键词: 2599; Tissue; type; responses; Mechanisms

Type 2 immune responses, defined by a dominant milieu of the cytokines IL-4, IL-5 and IL-13, are mounted in response to helminthic parasites, hematophagous ectoparasites (e.g. ticks) and venoms. Defense against these challenges, however, may not represent the original functions of type 2 immunity since these responses have been increasingly linked with tissue repair and regeneration, metabolic homeostasis and cold adaptation. Our proposal aims to elucidate the fundamental mechanisms that induce and regulate type 2 immunity in normal tissues and in pathologies where type 2 immunity is required for protection, or is itself the driver of disease.The term ‘type 2 response’ embraces both the innate type 2 response of tissues and the adaptive TH2 and IgE responses. While adaptive TH2 and IgE-mediated immunity have been extensively studied, the rules that govern the polarization of innate responses of the different tissues remain unclear. However, it is these innate tissue responses, which educate emigrating dendritic cells, and thereby dictate the class of adaptive response (e.g. TH1, TH2 or TH17) initiated in tissue-draining lymphatic organs. Why tissues mount type 2 responses to particular challenges, but not to others, is incompletely understood, but at the same time, one of the most urgent questions in current medical research because unbalanced type 2 immune responses are central pathogenic events in atopic and fibrotic diseases. Elucidating control pathways of innate type 2 tissue responses is key to unravel causes of inappropriate IgE production in allergic diseases, as well as to understanding type 2 immunity in pathogen defense, fibrotic and metabolic disease. Insight into control of type 2 responses of tissues is required to understand how tissues repair and regenerate under the influence of tissue-specific protective immune responses.By our collaborative approach, we hope to make a major contribution to understanding how the various tissue cells interact to mount and regulate a local type 2 response in steady state or under conditions of tissue stress of different nature and intensity.

由细胞因子IL-4、IL-5和IL-13的优势环境定义的2型免疫应答响应于蠕虫寄生虫、吸血性体外寄生虫（例如蜱）和毒液而建立。然而，对这些挑战的防御可能并不代表2型免疫的原始功能，因为这些反应越来越多地与组织修复和再生，代谢稳态和冷适应有关。我们的建议旨在阐明诱导和调节2型免疫的基本机制，在正常组织和病理学中，2型免疫是保护所必需的，或者本身是疾病的驱动力。术语“2型反应”包括组织的先天2型反应和适应性TH 2和IgE反应。虽然适应性TH 2和IgE介导的免疫已被广泛研究，但支配不同组织的先天反应的极化的规则仍不清楚。然而，正是这些先天性组织应答，教育了迁移的树突细胞，从而决定了在组织引流淋巴器官中引发的适应性应答的类别（例如TH 1、TH 2或TH 17）。为什么组织对特定的挑战产生2型反应，而不是对其他挑战产生2型反应，目前还不完全清楚，但同时，这是当前医学研究中最紧迫的问题之一，因为不平衡的2型免疫反应是特应性和纤维化疾病的中心致病事件。阐明先天2型组织反应的控制途径是解开过敏性疾病中不适当IgE产生的原因以及理解病原体防御、纤维化和代谢性疾病中的2型免疫的关键。需要深入了解组织2型反应的控制，以了解组织如何在组织特异性保护性免疫反应的影响下修复和再生。通过我们的合作方法，我们希望为了解各种组织细胞如何相互作用做出重大贡献。在稳态或不同性质和强度的组织应激条件下，启动和调节局部2型反应。