Sodium as factor controlling the threshold of autoimmune arthritis

钠作为控制自身免疫性关节炎阈值的因素

• 批准号: 418295881
• 负责人: Professor Dr. Martin Herrmann, since 7/2022
• 金额: --
• 依托单位: Medizinische Klinik 3 - Rheumatologie und Immunologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418295881?language=en
• 关键词: Sodium; factor; controlling; threshold; autoimmune

Sodium concentration in the extracellular milieu reportedly affects key aspects of both the innate and the adaptive immune response. However, a potential role of sodium and tissue tonicity during induction of autoimmunity and inflammation in experimental arthritis and human rheumatoid arthritis (RA) is still elusive. We have shown that feeding high salt diet increases skin tonicity in mice and simultaneously fosters both pathogen-triggered inflammation as well as sterile inflammatory processes such as zymosan-induced arthritis. Although underlying molecular mechanisms are still incompletely understood, p38-dependent activation of NFAT5/TonEBP/OREBP and altered transcription of osmo-protective genes are likely to be cardinally involved. The aim of this proposal is to analyze the role of tissue tonicity in the induction and onset of the inflammatory response in arthritis, where we will mechanistically focus on its impact on neutrophils and neutrophil extracellular trap formation and aggregation.

据报道，细胞外环境中的钠浓度影响先天和适应性免疫反应的关键方面。然而，在实验性关节炎和人类类风湿关节炎（RA）中，钠和组织强直在诱导自身免疫和炎症中的潜在作用仍然难以捉摸。我们已经证明，喂养高盐饮食增加了小鼠的皮肤张力，同时促进了病原体引发的炎症和无菌炎症过程，如酶生酶诱导的关节炎。尽管潜在的分子机制尚不完全清楚，但p38依赖的NFAT5/TonEBP/OREBP激活和渗透保护基因的转录改变可能是主要原因。本提案的目的是分析组织强直性在关节炎炎症反应的诱导和发作中的作用，其中我们将机械地关注其对中性粒细胞和中性粒细胞胞外陷阱形成和聚集的影响。