Bushra Alghamdi, Min Liu, Xin Huang, Rahul Debnath, Hamideh Afzali, Michael Troka, Akira Hasuike, Quinn Easter, Mi Zhou, Kevin Byrd, Michael Gonzalez, Kang I Ko, Dana T Graves
{"title":"单细胞RNA谱鉴定糖尿病相关粘膜炎症中免疫细胞群的变化。","authors":"Bushra Alghamdi, Min Liu, Xin Huang, Rahul Debnath, Hamideh Afzali, Michael Troka, Akira Hasuike, Quinn Easter, Mi Zhou, Kevin Byrd, Michael Gonzalez, Kang I Ko, Dana T Graves","doi":"10.1016/j.mucimm.2025.06.008","DOIUrl":null,"url":null,"abstract":"<p><p>Poorly controlled diabetes significantly worsens periodontal disease, affecting millions worldwide, yet the mechanisms driving this destructive synergy remain unclear. We generated single-cell RNA sequencing profiles of diabetic periodontal tissue, revealing increased γ<sup>δ</sup> T-cells, a loss of Tregs and greater neutrophil polarization as key mediators of diabetes-enhanced periodontitis. Flow cytometry confirmed significant expansion of IL-17A<sup>+</sup> γ<sup>δ+</sup> T-cells and reduced Tregs in diabetic mice, with parallel findings of elevated CD3<sup>+</sup>IL-17A<sup>+</sup> cells and reduced Tregs in human diabetic periodontal specimens. scRNAseq determined that diabetes caused a global increase in pro-inflammatory and a decrease in pro-resolving transcripts and enhanced inflammatory neutrophil polarization. Selective γ<sup>δ</sup> T-cell inhibition reversed diabetes-enhanced periodontal destruction while minimally affecting normoglycemic controls and returned neutrophil infiltration to normoglycemic levels. These findings point to unique aspects of diabetes-induced dysregulation, and implicate γ<sup>δ</sup> T-cells as a driving factor and point to them as a potential therapeutic target in periodontitis and other diabetic complications.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Single-cell RNA profiling identifies immune cell population shifts in diabetes associated mucosal inflammation.\",\"authors\":\"Bushra Alghamdi, Min Liu, Xin Huang, Rahul Debnath, Hamideh Afzali, Michael Troka, Akira Hasuike, Quinn Easter, Mi Zhou, Kevin Byrd, Michael Gonzalez, Kang I Ko, Dana T Graves\",\"doi\":\"10.1016/j.mucimm.2025.06.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Poorly controlled diabetes significantly worsens periodontal disease, affecting millions worldwide, yet the mechanisms driving this destructive synergy remain unclear. We generated single-cell RNA sequencing profiles of diabetic periodontal tissue, revealing increased γ<sup>δ</sup> T-cells, a loss of Tregs and greater neutrophil polarization as key mediators of diabetes-enhanced periodontitis. Flow cytometry confirmed significant expansion of IL-17A<sup>+</sup> γ<sup>δ+</sup> T-cells and reduced Tregs in diabetic mice, with parallel findings of elevated CD3<sup>+</sup>IL-17A<sup>+</sup> cells and reduced Tregs in human diabetic periodontal specimens. scRNAseq determined that diabetes caused a global increase in pro-inflammatory and a decrease in pro-resolving transcripts and enhanced inflammatory neutrophil polarization. Selective γ<sup>δ</sup> T-cell inhibition reversed diabetes-enhanced periodontal destruction while minimally affecting normoglycemic controls and returned neutrophil infiltration to normoglycemic levels. These findings point to unique aspects of diabetes-induced dysregulation, and implicate γ<sup>δ</sup> T-cells as a driving factor and point to them as a potential therapeutic target in periodontitis and other diabetic complications.</p>\",\"PeriodicalId\":18877,\"journal\":{\"name\":\"Mucosal Immunology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mucosal Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.mucimm.2025.06.008\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mucosal Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.mucimm.2025.06.008","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Single-cell RNA profiling identifies immune cell population shifts in diabetes associated mucosal inflammation.
Poorly controlled diabetes significantly worsens periodontal disease, affecting millions worldwide, yet the mechanisms driving this destructive synergy remain unclear. We generated single-cell RNA sequencing profiles of diabetic periodontal tissue, revealing increased γδ T-cells, a loss of Tregs and greater neutrophil polarization as key mediators of diabetes-enhanced periodontitis. Flow cytometry confirmed significant expansion of IL-17A+ γδ+ T-cells and reduced Tregs in diabetic mice, with parallel findings of elevated CD3+IL-17A+ cells and reduced Tregs in human diabetic periodontal specimens. scRNAseq determined that diabetes caused a global increase in pro-inflammatory and a decrease in pro-resolving transcripts and enhanced inflammatory neutrophil polarization. Selective γδ T-cell inhibition reversed diabetes-enhanced periodontal destruction while minimally affecting normoglycemic controls and returned neutrophil infiltration to normoglycemic levels. These findings point to unique aspects of diabetes-induced dysregulation, and implicate γδ T-cells as a driving factor and point to them as a potential therapeutic target in periodontitis and other diabetic complications.
期刊介绍:
Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.