Interplay of innate lymphoid cells and regulatory T cells in NLRP3 inflammasome-dependent nephritis

先天淋巴细胞和调节性 T 细胞在 NLRP3 炎症小体依赖性肾炎中的相互作用

• 批准号: 320317112
• 负责人: Dr. Isis Ludwig-Portugall
• 金额: --
• 依托单位: Institut für Experimentelle Immunologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/320317112?language=en
• 关键词: Interplay; innate; lymphoid; cells; regulatory

Inflammasome-induced nephritis is mainly triggered by activated dendritic cells and macrophages via the production of pro-inflammatory cytokines such as IL-1b, TNF, IL-6 and IL-18. Preliminary experiments suggest a connection between inflammation on the composition of innate lymphoid cells in the kidney. ILC seem to promote an inflamed environment by enhancing the inflammatory process and by interacting with CD4+ T helper cells. The composition of cytokines suggested a permissive environment for Th17 lymphocytes during kidney inflammation, but it may also induce innate lymphoid cells especially of subpopulation 3. This project will investigate the interplay of regulatory T cells and ILC in NLRP3-inflammasome-induced kidney inflammation. Here, we will specifically focus on the role of NLRP3-inflammasome-induced cytokines on the activation and plasticity of the renal ILC populations. In particular, we will investigate the local and systemic effects of inflammation and inflammatory cytokines on the function and composition renal and splenic ILCs. Furthermore, the suppressive or modulating capacity of Tregs and the underlying mechanism of Tregs on renal ILCs will be elucidated.

炎性小体诱导的肾炎主要由活化的树突状细胞和巨噬细胞通过产生促炎细胞因子如IL-1b、TNF、IL-6和IL-18触发。初步实验表明，炎症与肾脏中先天淋巴细胞的组成之间存在联系。ILC似乎通过增强炎症过程和通过与CD 4 + T辅助细胞相互作用来促进炎症环境。细胞因子的组成表明，在肾脏炎症过程中Th 17淋巴细胞的一个宽松的环境，但它也可能诱导先天性淋巴细胞，特别是亚群3。该项目将研究调节性T细胞和ILC在NLRP 3-炎性小体诱导的肾脏炎症中的相互作用。在这里，我们将特别关注NLRP 3-炎性体诱导的细胞因子对肾ILC群体的激活和可塑性的作用。特别是，我们将研究炎症和炎性细胞因子对肾和脾ILC的功能和组成的局部和全身作用。此外，Tcl 4对肾ILCs的抑制或调节能力以及Tcl 4对肾ILCs的潜在机制将被阐明。