A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren's Syndrome.
A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren's Syndrome.
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原发性干燥综合征线粒体功能障碍与唾液腺免疫微环境之间的联系
DOI：
10.3389/fimmu.2022.845209
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发表时间：
2022
影响因子：
7.3
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Li N;Li Y;Hu J;Wu Y;Yang J;Fan H;Li L;Luo D;Ye Y;Gao Y;Xu H;Hai W;Jiang L
原发性干燥综合征（pSS）是一种缓慢进展的炎性自身免疫性疾病，其特征是淋巴细胞浸润到唾液腺和泪腺中。越来越多的人认识到，上皮线粒体的形态学改变参与pSS患者细胞生物能量学的改变。线粒体在pSS发病机制和异常免疫微环境中的作用的综合分析仍然未知。从MitoMiner、MitoCarta和NCBI GEO数据库中下载了Escherichia相关基因和基因表达数据。我们进行了新的转录组学分析，并通过计算机辅助算法构建了PSS-唾液腺中线粒体功能和免疫微环境之间的网络。随后，在临床样本中进行实时PCR，以验证生物信息学结果。进一步研究了非pSS和pSS患者的唇唾液腺样本的组织学染色和透射电子显微镜（TEM），其特征在于在疾病的不同阶段的唾液腺相关表型观察。生物信息学分析表明，几个与pSS相关的基因的表达发生了变化。实时荧光定量PCR结果显示，pSS临床样本中CD38、CMPK2、TBC1D9和PYCR1四个hub基因的表达存在差异。这些枢纽基因与唾液腺中免疫细胞浸润程度、线粒体呼吸链复合物、线粒体代谢途径、TCA循环和pSS中丙酮酸/酮/脂质/氨基酸代谢相关。临床数据显示，pSS样本中裂变（Fis1、DRP 1和MFF）和融合（MFN 1、MFN 2和OPA 1）的基因表达下调，与公共验证数据库的结果一致。随着疾病的进展，细胞色素c和Bcl-2蛋白在pSS患者的唾液腺中呈区域性分布。透射电镜显示唾液腺上皮细胞胞浆脂滴和进行性肿胀的线粒体。我们的研究揭示了pSS患者唾液腺中线粒体功能障碍与免疫微环境之间的相互作用，这可能为基于线粒体功能调节的SS临床管理提供重要见解。
Primary Sjogren’s syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It becomes more recognized that morphology alterations of epithelial mitochondria are involved in altered cellular bioenergetics in pSS patients. The integrated analysis of the mitochondrial role in the pathogenesis and aberrant immune microenvironment in pSS remains unknown. The mitochondria-related genes and gene expression data were downloaded from the MitoMiner, MitoCarta, and NCBI GEO databases. We performed novel transcriptomic analysis and constructed a network between the mitochondrial function and immune microenvironment in pSS-salivary glands by computer-aided algorithms. Subsequently, real-time PCR was performed in clinical samples in order to validate the bioinformatics results. Histological staining and transmission electron microscopy (TEM) were further studied on labial salivary gland samples of non-pSS and pSS patients characterized for mitochondria-related phenotypic observation in the different stages of the disease. The bioinformatic analysis revealed that the expression of several mitochondria-related genes was altered in pSS. Quantitative real-time PCR showed that four hub genes, CD38, CMPK2, TBC1D9, and PYCR1, were differentially expressed in the pSS clinical samples. These hub genes were associated with the degree of immune cell infiltration in salivary glands, the mitochondrial respiratory chain complexes, mitochondrial metabolic pathway in gluconeogenesis, TCA cycle, and pyruvate/ketone/lipid/amino acid metabolism in pSS. Clinical data revealed that the gene expression of fission (Fis1, DRP1, and MFF) and fusion (MFN1, MFN2, and OPA1) was downregulated in pSS samples, consistent with the results from the public validation database. As the disease progressed, cytochrome c and Bcl-2 proteins were regionally distributed in salivary glands from pSS patients. TEM revealed cytoplasmic lipid droplets and progressively swollen mitochondria in salivary epithelial cells. Our study revealed cross talk between mitochondrial dysfunction and the immune microenvironment in salivary glands of pSS patients, which may provide important insights into SS clinical management based on modulation of mitochondrial function.
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影响因子：
20.8
作者：
Chini CCS;Peclat TR;Warner GM;Kashyap S;Espindola-Netto JM;de Oliveira GC;Gomez LS;Hogan KA;Tarragó MG;Puranik AS;Agorrody G;Thompson KL;Dang K;Clarke S;Childs BG;Kanamori KS;Witte MA;Vidal P;Kirkland AL;De Cecco M;Chellappa K;McReynolds MR;Jankowski C;Tchkonia T;Kirkland JL;Sedivy JM;van Deursen JM;Baker DJ;van Schooten W;Rabinowitz JD;Baur JA;Chini EN
通讯作者：
Chini EN
影响因子：
7.3
作者：
Eleftheriadis T;Pissas G;Liakopoulos V;Stefanidis I
通讯作者：
Stefanidis I
通过瞬时 BCL-XL 过表达，在人类多能干细胞中通过 CRISPR-Cas9 实现高效基因组编辑
影响因子：
14.9
作者：
Li XL;Li GH;Fu J;Fu YW;Zhang L;Chen W;Arakaki C;Zhang JP;Wen W;Zhao M;Chen WV;Botimer GD;Baylink D;Aranda L;Choi H;Bechar R;Talbot P;Sun CK;Cheng T;Zhang XB
通讯作者：
Zhang XB
影响因子：
6.6
作者：
Guillot, Gilles;Rousset, Francois
通讯作者：
Rousset, Francois
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J