代谢物衍生型损伤相关分子模式与自身免疫相关疾病

Metabolism associated molecular patterns and autoimmune diseases

损伤相关分子模式(damage associated molecular patterns,DAMPs)通常起源于受损细胞的内源性成分,并且通过激活机体细胞上的DAMPs感受器来引发细胞活化和后续炎症反应等.未能被及时清除的DAMPs可能会导致持续的炎症,从而促进免疫相关疾病的发生和进展.目前,关于DAMPs的研究论述已全面深入.本文综述了一类基于代谢物衍生分子的DAMPs(metabolism associated molecular patterns,MAMPs),即源自脂质、葡萄糖、核苷酸和氨基酸的代谢衍生分子来源的DAMPs.本文总结这类MAMPs在促进炎症反应中的分子机制,同时也对其参与的自身免疫相关疾病进行初步的探讨.此外,本综述以系统性红斑狼疮,类风湿关节炎,炎症性肠病等自身免疫相关疾病为例,对以MAMPs为靶点的潜在新型治疗策略进行深入剖析.综上所述,本文总结MAMPs的研究现状,同时提出以MAMPs为靶点针对免疫相关疾病的靶向治疗措施和药物提供新的见解.

Damage-associated molecular patterns(DAMPs)are endogenous molecules typically released from damaged or stressed cells that trigger inflammatory responses by activating DAMP receptors on immune cells.If these DAMPs are not promptly cleared,sustained inflammation can ensue,promoting the development and progression of autoimmune diseases.This review provides an in-depth overview of a specific class of metabolite-derived DAMPs,known as metabolismassociated molecular patterns(MAMPs).These MAMPs are derived from the metabolic pathways governing lipids,glucose,nucleotides,and amino acids.The molecular mechanisms by which these MAMPs contribute to inflammatory responses are thoroughly summarized,accompanied by a comprehensive exploration of their role in autoimmune diseases.The review begins by highlighting the critical role of MAMPs in initiating and sustaining inflammatory processes.Uncleared MAMPs can drive chronic inflammation,a hallmark of many autoimmune diseases.The authors then delve into the specific class of MAMPs,detailing how metabolites from lipid,glucose,nucleotide,and amino acid pathways can function as DAMPs.Through a detailed examination of the molecular mechanisms,the review elucidates how these MAMPs interact with receptors on immune cells to trigger inflammatory cascades.This provides important insights into the pathogenic contributions of MAMPs to the development and progression of autoimmune disorders.Shifting the focus to potential therapeutic interventions,the review analyzes emerging strategies that target MAMPs.Using systemic lupus erythematosus,rheumatoid arthritis,multiple sclerosis,inflammatory bowel disease,and other autoimmune diseases as illustrative cases,the authors discuss how disrupting MAMP-receptor interactions or enhancing MAMP clearance could offer novel avenues for more precise,targeted treatment of these autoimmune conditions.The review delves deeper into the specific mechanisms by which MAMPs derived from lipid,glucose,nucleotide,and amino acid metabolism,covering lipid metabolisms(farnesyl diphosphate(FPP),geranylgeranyl diphosphate(GGPP),oxidized low-density lipoproteins(OxLDLs),cholesterol crystals,bile acids(BA),and saturated fatty acids(SFAs)),glucose metabolisms(glucose,advanced glycation end products(AGEs),and citrate),nucleotide metabolisms(ATP and uric acid crystal),and amino acid metabolisms(glutamate).By comprehensively exploring these diverse metabolic pathways and their associated MAMPs,the review provides a holistic understanding of the complex interplay between metabolism and immune dysregulation in autoimmune diseases.This knowledge is crucial for the development of targeted therapies that can address the underlying metabolic disturbances contributing to chronic inflammation and autoimmunity.In conclusion,the review’s in-depth exploration of how MAMPs derived from lipid,glucose,nucleotide,and amino acid metabolic pathways can trigger inflammatory responses and contribute to the development and progression of autoimmune diseases provides crucial insights.By elucidating the molecular mechanisms underlying MAMP-mediated immune activation,the authors identify promising new avenues for therapeutic intervention.This comprehensive review presents a timely and insightful summary of the current research landscape surrounding MAMPs and their pivotal role in autoimmune disorders.By offering novel perspectives on the pathogenic mechanisms and potential therapeutic targeting of these metabolite-derived DAMPs,the review lays the groundwork for the advancement of more personalized and effective treatments for a wide range of autoimmune conditions.