Yiming Shen, Ruiya Shi, ShiPing Lu, Yan Wang, Ziqi Zhou, Chenhua Wu, Qi You, Hongye Fan, Jie Wu
{"title":"肽基精氨酸脱氨酶 4 依赖性巨噬细胞胞外陷阱的形成对 1 型糖尿病发病机制的作用","authors":"Yiming Shen, Ruiya Shi, ShiPing Lu, Yan Wang, Ziqi Zhou, Chenhua Wu, Qi You, Hongye Fan, Jie Wu","doi":"10.2337/db23-1000","DOIUrl":null,"url":null,"abstract":"<p><p>Excessive formation of macrophage extracellular trap (MET) has been implicated in several autoimmune disease pathogeneses; however, its impact on type 1 diabetes (T1D) and related mechanisms remains enigmatic. We demonstrated the pivotal role of peptidyl arginine deiminase 4 (PAD4) in driving profuse MET formation and macrophage M1 polarization in intestinal inflammation in NOD mice. Genetic knockout of PAD4 or adoptive transfer of METs altered the proportion of proinflammatory T cells in the intestine, subsequently influencing their migration to the pancreas. Combining RNA sequencing and CUT&Tag analysis, we found activated PAD4 transcriptionally regulated CXCL10 expression. This study comprehensively investigated how excessive PAD4-mediated MET formation in the colon increases the aggravation of intestinal inflammation and proinflammatory T-cell migration and finally is involved in T1D progression, suggesting that inhibition of MET formation may be a potential therapeutic target in T1D.</p><p><strong>Article highlights: </strong></p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1862-1874"},"PeriodicalIF":0.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Role of Peptidyl Arginine Deiminase 4-Dependent Macrophage Extracellular Trap Formation in Type 1 Diabetes Pathogenesis.\",\"authors\":\"Yiming Shen, Ruiya Shi, ShiPing Lu, Yan Wang, Ziqi Zhou, Chenhua Wu, Qi You, Hongye Fan, Jie Wu\",\"doi\":\"10.2337/db23-1000\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Excessive formation of macrophage extracellular trap (MET) has been implicated in several autoimmune disease pathogeneses; however, its impact on type 1 diabetes (T1D) and related mechanisms remains enigmatic. We demonstrated the pivotal role of peptidyl arginine deiminase 4 (PAD4) in driving profuse MET formation and macrophage M1 polarization in intestinal inflammation in NOD mice. Genetic knockout of PAD4 or adoptive transfer of METs altered the proportion of proinflammatory T cells in the intestine, subsequently influencing their migration to the pancreas. Combining RNA sequencing and CUT&Tag analysis, we found activated PAD4 transcriptionally regulated CXCL10 expression. This study comprehensively investigated how excessive PAD4-mediated MET formation in the colon increases the aggravation of intestinal inflammation and proinflammatory T-cell migration and finally is involved in T1D progression, suggesting that inhibition of MET formation may be a potential therapeutic target in T1D.</p><p><strong>Article highlights: </strong></p>\",\"PeriodicalId\":93977,\"journal\":{\"name\":\"Diabetes\",\"volume\":\" \",\"pages\":\"1862-1874\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2337/db23-1000\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2337/db23-1000","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Role of Peptidyl Arginine Deiminase 4-Dependent Macrophage Extracellular Trap Formation in Type 1 Diabetes Pathogenesis.
Excessive formation of macrophage extracellular trap (MET) has been implicated in several autoimmune disease pathogeneses; however, its impact on type 1 diabetes (T1D) and related mechanisms remains enigmatic. We demonstrated the pivotal role of peptidyl arginine deiminase 4 (PAD4) in driving profuse MET formation and macrophage M1 polarization in intestinal inflammation in NOD mice. Genetic knockout of PAD4 or adoptive transfer of METs altered the proportion of proinflammatory T cells in the intestine, subsequently influencing their migration to the pancreas. Combining RNA sequencing and CUT&Tag analysis, we found activated PAD4 transcriptionally regulated CXCL10 expression. This study comprehensively investigated how excessive PAD4-mediated MET formation in the colon increases the aggravation of intestinal inflammation and proinflammatory T-cell migration and finally is involved in T1D progression, suggesting that inhibition of MET formation may be a potential therapeutic target in T1D.
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