CD8(+) T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs

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dc.contributor.author Zhang, Kaiyi
dc.contributor.author Tao, Cong
dc.contributor.author Xu, Jianping
dc.contributor.author Ruan, Jinxue
dc.contributor.author Xia, Jihan
dc.contributor.author Zhu, Wenjuan
dc.contributor.author Xin, Leilei
dc.contributor.author Ye, Huaqiong
dc.contributor.author Xie, Ning
dc.contributor.author Xia, Boce
dc.contributor.author Li, Chenxiao
dc.contributor.author Wu, Tianwen
dc.contributor.author Wang, Yanfang
dc.contributor.author Schroyen, Martine
dc.contributor.author Xiao, Xinhua
dc.contributor.author Fan, Jiangao
dc.contributor.author Yang, Shulin
dc.date.accessioned 2021-09-17T06:37:02Z
dc.date.available 2021-09-17T06:37:02Z
dc.date.issued 2021-07-12
dc.identifier.citation Zhang , K , Tao , C , Xu , J , Ruan , J , Xia , J , Zhu , W , Xin , L , Ye , H , Xie , N , Xia , B , Li , C , Wu , T , Wang , Y , Schroyen , M , Xiao , X , Fan , J & Yang , S 2021 , ' CD8(+) T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs ' , Frontiers in Immunology , vol. 12 , 690069 . https://doi.org/10.3389/fimmu.2021.690069
dc.identifier.other PURE: 168537739
dc.identifier.other PURE UUID: 3e2443e5-fb63-4c82-8907-702616fe2342
dc.identifier.other WOS: 000680571400001
dc.identifier.other ORCID: /0000-0002-0035-0727/work/100132609
dc.identifier.uri http://hdl.handle.net/10138/334431
dc.description.abstract Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPR(dn) , hIAPP and PNPLA3(I148M) . Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8(+) T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs' liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases. en
dc.format.extent 16
dc.language.iso eng
dc.relation.ispartof Frontiers in Immunology
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject pig model(s)
dc.subject metaflammation
dc.subject CD8
dc.subject T cells
dc.subject liver inflammation
dc.subject obesity
dc.subject adipose tissue
dc.subject INSULIN-RESISTANCE
dc.subject GENETIC-VARIATION
dc.subject MODELS
dc.subject OBESITY
dc.subject PNPLA3
dc.subject STEATOHEPATITIS
dc.subject METAFLAMMATION
dc.subject SUSCEPTIBILITY
dc.subject GLUCOSE
dc.subject ANTIGEN
dc.subject 3111 Biomedicine
dc.title CD8(+) T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs en
dc.type Article
dc.contributor.organization Faculty of Medicine
dc.contributor.organization University of Helsinki
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3389/fimmu.2021.690069
dc.relation.issn 1664-3224
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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