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

doi:10.4049/jimmunol.2100313

HFCAS OpenIR

	Adipocyte CD1d Gene Transfer Induces T Cell Expansion andAdipocyte Inflammation in CD1d Knockout Mice
	Xiao, Run 1,2,7; Mansour, Anthony G.3,4; Huang, Wei1,2 ; Hassan, Quais N.1,2,5; Wilkins, Ryan K.1,2; Komatineni, Suraj, V 1,2; Bates, Rhiannon 1,2; Ali, Seemaab 1,2,5; Chrislip, Logan A.1,2; Queen, Nicholas J.1,2; Ma, Shoubao 3,4; Yu, Jianhua 3,4; Lordo, Matthew R.2,5; Mundy-Bosse, Bethany L.2,6; Caligiuri, Michael A.3,4; Cao, Lei1,2
	2022-05-01
发表期刊	JOURNAL OF IMMUNOLOGY
ISSN	0022-1767
通讯作者	Caligiuri, Michael A.(mcaligiuri@coh.org) ; Cao, Lei(lei.cao@osumc.edu)
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.
DOI	10.4049/jimmunol.2100313
关键词[WOS]	ADIPOSE-TISSUE INFLAMMATION ; DIET-INDUCED OBESITY ; INSULIN-RESISTANCE ; NKT CELLS ; IMMUNE-RESPONSES ; EPITHELIAL CD1D ; PPAR-GAMMA ; MOUSE CD1 ; ACTIVATION ; HOMEOSTASIS
收录类别	SCI
语种	英语
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]
项目资助者	National Institutes of Health
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000795780300005
出版者	AMER ASSOC IMMUNOLOGISTS
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/130928
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.Ohio State Univ, Coll Med, Dept Canc Biol & Genet, Columbus, OH 43210 USA 2.Ohio State Univ, James Canc Hosp & Solove Res Inst, Comprehens Canc Ctr, Columbus, OH 43210 USA 3.City Hope Natl Med Ctr, Dept Hematol Malignancies & Stem Cell Transplanta, Los Angeles, CA 91010 USA 4.Beckman Res Inst, Los Angeles, CA 91010 USA 5.Ohio State Univ, Med Scientist Training Program, Columbus, OH 43210 USA 6.Ohio State Univ, Dept Internal Med, Div Hematol, Wexner Med Ctr, Columbus, OH 43210 USA 7.Chinese Acad Sci, Canc Hosp, Univ Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou, Zhejiang, Peoples R China
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).