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Adipocyte CD1d Gene Transfer Induces T Cell Expansion andAdipocyte Inflammation in CD1d Knockout Mice

文献类型：期刊论文

作者Xiao, Run1,2,3; Mansour, Anthony G.4,5; Huang, Wei2,3; Hassan, Quais N.2,3,6; Wilkins, Ryan K.2,3; Komatineni, Suraj, V2,3; Bates, Rhiannon2,3; Ali, Seemaab2,3,6; Chrislip, Logan A.2,3; Queen, Nicholas J.2,3
刊名JOURNAL OF IMMUNOLOGY
出版日期2022-05-01
卷号208
ISSN号0022-1767
DOI10.4049/jimmunol.2100313
通讯作者Caligiuri, Michael A.(mcaligiuri@coh.org) ; Cao, Lei(lei.cao@osumc.edu)
英文摘要CD1d, a lipid Ag-presenting molecule for invariant NKT (iNKT) cells, is abundantly expressed on adipocytes and regulatesadipose homeostasis through iNKT cells. CD1d gene expression was restored in visceral adipose tissue adipocytes of CD1dknockout (KO) mice to investigate the interactions between adipocytes and immune cells within adipose tissue. We developed anadipocyte-specific targeting recombinant adeno-associated viral vector, with minimal off-target transgene expression in the liver,to rescue CD1d gene expression in visceral adipose tissue adipocytes of CD1d KO mice, followed by assessment of immune cellalternations in adipose tissue and elucidation of the underlying mechanisms of alteration. We report that adeno-associatedvirus??mediated gene transfer of CD1d to adipocytes in CD1d KO mice fails to rescue iNKT cells but leads to massive and selectiveexpansion of T cells within adipose tissue, particularly CD8+T effector cells, that is associated with adipocyte NLRP3inflammasome activation, dysregulation of adipocyte functional genes, and upregulation of apoptotic pathway proteins. AnNLRP3 inhibitor has no effect on T cell phenotypes whereas depletion of CD8+T cells significantly attenuates inflammasomeactivation and abolishes the dysregulation of adipocyte functional genes induced by adipocyte CD1d. In contrast, adipocyteoverexpression of CD1d fails to induce T cell activation in wild-type mice or in invariant TCRa-chain Ja18 KO mice that have anormal lymphocyte repertoire except for iNKT cells. Our studies uncover an adipocyte CD1dfiCD8+T cellfiadipocyteinflammasome cascade, in which CD8+T cells function as a key mediator of adipocyte inflammation likely induced by anallogeneic response against the CD1d molecule.The Journal of Immunology, 2022, 208: 2109??2121.
WOS关键词ADIPOSE-TISSUE INFLAMMATION ; DIET-INDUCED OBESITY ; INSULIN-RESISTANCE ; NKT CELLS ; IMMUNE-RESPONSES ; EPITHELIAL CD1D ; PPAR-GAMMA ; MOUSE CD1 ; ACTIVATION ; HOMEOSTASIS
资助项目National Institutes of Health[CA163640] ; National Institutes of Health[CA166590] ; National Institutes of Health[AG041250] ; National Institutes of Health[CA163205] ; National Institutes of Health[CA068458] ; National Institutes of Health[CA185301] ; National Institutes of Health[CA210087]
WOS研究方向Immunology
语种英语
出版者AMER ASSOC IMMUNOLOGISTS
WOS记录号WOS:000795780300005
资助机构National Institutes of Health
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/130927]  
专题中国科学院合肥物质科学研究院
通讯作者Caligiuri, Michael A.; Cao, Lei
作者单位1.Chinese Acad Sci, Canc Hosp, Univ Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou, Zhejiang, Peoples R China
2.Ohio State Univ, Coll Med, Dept Canc Biol & Genet, Columbus, OH 43210 USA
3.Ohio State Univ, James Canc Hosp & Solove Res Inst, Comprehens Canc Ctr, Columbus, OH 43210 USA
4.City Hope Natl Med Ctr, Dept Hematol Malignancies & Stem Cell Transplanta, Los Angeles, CA 91010 USA
5.Beckman Res Inst, Los Angeles, CA 91010 USA
6.Ohio State Univ, Med Scientist Training Program, Columbus, OH 43210 USA
7.Ohio State Univ, Dept Internal Med, Div Hematol, Wexner Med Ctr, Columbus, OH 43210 USA
推荐引用方式
GB/T 7714		 Xiao, Run,Mansour, Anthony G.,Huang, Wei,et al. Adipocyte CD1d Gene Transfer Induces T Cell Expansion andAdipocyte Inflammation in CD1d Knockout Mice[J]. JOURNAL OF IMMUNOLOGY,2022,208.
APA Xiao, Run.,Mansour, Anthony G..,Huang, Wei.,Hassan, Quais N..,Wilkins, Ryan K..,...&Cao, Lei.(2022).Adipocyte CD1d Gene Transfer Induces T Cell Expansion andAdipocyte Inflammation in CD1d Knockout Mice.JOURNAL OF IMMUNOLOGY,208.
MLA Xiao, Run,et al."Adipocyte CD1d Gene Transfer Induces T Cell Expansion andAdipocyte Inflammation in CD1d Knockout Mice".JOURNAL OF IMMUNOLOGY 208(2022).

入库方式： OAI收割

来源：合肥物质科学研究院

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