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

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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

Titel: CD8(+) T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs
Författare: Zhang, Kaiyi; Tao, Cong; Xu, Jianping; Ruan, Jinxue; Xia, Jihan; Zhu, Wenjuan; Xin, Leilei; Ye, Huaqiong; Xie, Ning; Xia, Boce; Li, Chenxiao; Wu, Tianwen; Wang, Yanfang; Schroyen, Martine; Xiao, Xinhua; Fan, Jiangao; Yang, Shulin
Upphovmannens organisation: Faculty of Medicine
University of Helsinki
Datum: 2021-07-12
Språk: eng
Sidantal: 16
Tillhör serie: Frontiers in Immunology
ISSN: 1664-3224
DOI: https://doi.org/10.3389/fimmu.2021.690069
Permanenta länken (URI): http://hdl.handle.net/10138/334431
Abstrakt: 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.
Subject: pig model(s)
metaflammation
CD8
T cells
liver inflammation
obesity
adipose tissue
INSULIN-RESISTANCE
GENETIC-VARIATION
MODELS
OBESITY
PNPLA3
STEATOHEPATITIS
METAFLAMMATION
SUSCEPTIBILITY
GLUCOSE
ANTIGEN
3111 Biomedicine
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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