Tim4 deficiency reduces CD301b+ macrophage and aggravates periodontitis bone loss.

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Ziming Wang, Hao Zeng, Can Wang, Jiaolong Wang, Jing Zhang, Shuyuan Qu, Yue Han, Liu Yang, Yueqi Ni, Wenan Peng, Huan Liu, Hua Tang, Qin Zhao, Yufeng Zhang
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Abstract

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss. With the progression of periodontitis, the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption. CD301b+ macrophages are specific to the osteoimmunology microenvironment, and are emerging as vital booster for conducting bone regeneration. However, the key upstream targets of CD301b+ macrophages and their potential mechanism in periodontitis remain elusive. In this study, we concentrated on the role of Tim4, a latent upstream regulator of CD301b+ macrophages. We first demonstrated that the transcription level of Timd4 (gene name of Tim4) in CD301b+ macrophages was significantly upregulated compared to CD301b- macrophages via high-throughput RNA sequencing. Moreover, several Tim4-related functions such as apoptotic cell clearance, phagocytosis and engulfment were positively regulated by CD301b+ macrophages. The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages. The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+ macrophages as periodontitis progressed. Furthermore, the deficiency of Tim4 in mice decreased CD301b+ macrophages and eventually magnified alveolar bone resorption in periodontitis. Additionally, Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+ macrophages phenotype. In a word, Tim4 might regulate CD301b+ macrophages through p38 MAPK signaling pathway in periodontitis, which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

Abstract Image

Tim4 缺乏会减少 CD301b+ 巨噬细胞,加重牙周炎骨质流失。
牙周炎是一种常见的慢性炎症性疾病,会造成牙周骨破坏,最终可能导致牙齿脱落。随着牙周炎的发展,牙周炎的骨免疫微环境遭到破坏,导致病理性牙槽骨吸收的形成。CD301b+ 巨噬细胞是骨免疫微环境的特异性巨噬细胞,正在成为促进骨再生的重要助推器。然而,CD301b+巨噬细胞的上游关键靶点及其在牙周炎中的潜在机制仍未确定。在本研究中,我们重点研究了 CD301b+ 巨噬细胞的潜伏上游调控因子 Tim4 的作用。我们首先通过高通量 RNA 测序证明,与 CD301b- 巨噬细胞相比,CD301b+ 巨噬细胞中 Timd4(Tim4 的基因名)的转录水平显著上调。此外,CD301b+巨噬细胞还对凋亡细胞清除、吞噬和吞噬等几种与Tim4相关的功能进行了正向调节。单细胞 RNA 测序分析随后发现,Cd301b 和 Timd4 在巨噬细胞中特异性共表达。随后的流式细胞分析表明,随着牙周炎的发展,巨噬细胞总数中的 Tim4 阳性表达率与 CD301b+ 巨噬细胞的比例呈高度同步的动态变化。此外,小鼠缺乏 Tim4 会减少 CD301b+ 巨噬细胞的数量,并最终加剧牙周炎的牙槽骨吸收。此外,Tim4 还能控制 p38 MAPK 信号通路,最终介导 CD301b+ 巨噬细胞的表型。总之,Tim4可能通过p38 MAPK信号通路调控牙周炎中的CD301b+巨噬细胞,这为牙周炎的免疫调节提供了新的视角,也有助于开发创新的牙周炎治疗靶点和治疗策略。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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