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。

IF 7.9 2区 医学 Q1 IMMUNOLOGY
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
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引用次数: 0

摘要

控制不良的糖尿病显著地将牙周病从可控制转变为晚期,影响全世界数百万人,但驱动这种破坏性协同作用的机制尚不清楚。为了研究这些病理相互作用,我们生成了糖尿病牙周组织的单细胞RNA测序图谱,揭示了γδ t细胞是以前未被识别的糖尿病增强牙周破坏的中心介质。流式细胞术验证证实,与血糖正常的小鼠相比,糖尿病小鼠体内产生IL-17A的γδ t细胞显著扩增,同时在人类糖尿病牙周标本中也发现IL-17A + 细胞升高。选择性γδ t细胞抑制可显著逆转糖尿病增强的牙周破坏,同时对正常血糖控制的影响最小,并使中性粒细胞浸润恢复到正常血糖水平。scRNAseq发现了其他因素,包括中性粒细胞向促炎表型的更大极化和treg的丢失。这些发现指出了糖尿病诱导失调的独特方面,并暗示γδ t细胞在这一过程中是一个驱动因素。结果还指出γδ t细胞是牙周炎和其他糖尿病并发症的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
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.
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