CD8+CD103+ iTregs Inhibit Chronic Graft-versus-Host Disease with Lupus Nephritis by the Increased Expression of CD39

Xiao Zhang; Xia Ouyang; Zhenjian Xu; Junzhe Chen; Qiuyan Huang; Ya Liu; Tongtong Xu; Julie Wang; Nancy Olsen; Anping Xu; Song Guo Zheng

doi:10.1016/j.ymthe.2019.07.014

CD8+CD103+ iTregs Inhibit Chronic Graft-versus-Host Disease with Lupus Nephritis by the Increased Expression of CD39

Xiao Zhang, Xia Ouyang, Zhenjian Xu, Junzhe Chen, Qiuyan Huang, Ya Liu, Tongtong Xu, Julie Wang, Nancy Olsen, Anping Xu, Song Guo Zheng

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Many patients with systemic lupus erythematosus (SLE) have lupus nephritis, one of the severe complications of SLE. We previously reported that CD8+CD103+ T regulatory cells induced ex vivo with transforming growth factor β (TGF-β) (iTregs) inhibited immune cells responses to ameliorate excessive autoimmune inflammation. However, the molecular mechanism(s) underlying the role of these CD8+ iTregs is still unclear. Here we identified that CD39, which is highly expressed on CD8+ iTregs, crucially contributes to the immunosuppressive role of the CD8+CD103+ iTregs. We showed that adoptive transfer of CD8+CD103+ iTregs significantly relieves the chronic graft-versus-host disease with lupus nephritis and CD39 inhibitor mostly abolished the functional activities of these CD8+ iTregs in vitro and in vivo. CD39+ cells sorted from CD8+CD103+ iTregs were more effective in treating lupus nephritis than CD39− partner cells in vivo. Furthermore, human CD8+ iTregs displayed increased CD103 and CD39 expressions, and CD39 was involved in the suppressive function of human CD8+ iTregs. Thus, our data implicated a crucial role of CD39 in CD8+CD103+ iTregs in treating lupus nephritis, and CD39 could be a new phenotypic biomarker for the identification of highly qualified CD8+ Tregs. This subpopulation may have therapeutic potential in patients with SLE nephritis and other autoimmune diseases.

Original language	English (US)
Pages (from-to)	1963-1973
Number of pages	11
Journal	Molecular Therapy
Volume	27
Issue number	11
DOIs	https://doi.org/10.1016/j.ymthe.2019.07.014
State	Published - Nov 6 2019

All Science Journal Classification (ASJC) codes

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

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10.1016/j.ymthe.2019.07.014

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@article{6b4a7cc8f1e74f4db78c8dcef0a25e38,

title = "CD8+CD103+ iTregs Inhibit Chronic Graft-versus-Host Disease with Lupus Nephritis by the Increased Expression of CD39",

abstract = "Many patients with systemic lupus erythematosus (SLE) have lupus nephritis, one of the severe complications of SLE. We previously reported that CD8+CD103+ T regulatory cells induced ex vivo with transforming growth factor β (TGF-β) (iTregs) inhibited immune cells responses to ameliorate excessive autoimmune inflammation. However, the molecular mechanism(s) underlying the role of these CD8+ iTregs is still unclear. Here we identified that CD39, which is highly expressed on CD8+ iTregs, crucially contributes to the immunosuppressive role of the CD8+CD103+ iTregs. We showed that adoptive transfer of CD8+CD103+ iTregs significantly relieves the chronic graft-versus-host disease with lupus nephritis and CD39 inhibitor mostly abolished the functional activities of these CD8+ iTregs in vitro and in vivo. CD39+ cells sorted from CD8+CD103+ iTregs were more effective in treating lupus nephritis than CD39− partner cells in vivo. Furthermore, human CD8+ iTregs displayed increased CD103 and CD39 expressions, and CD39 was involved in the suppressive function of human CD8+ iTregs. Thus, our data implicated a crucial role of CD39 in CD8+CD103+ iTregs in treating lupus nephritis, and CD39 could be a new phenotypic biomarker for the identification of highly qualified CD8+ Tregs. This subpopulation may have therapeutic potential in patients with SLE nephritis and other autoimmune diseases.",

author = "Xiao Zhang and Xia Ouyang and Zhenjian Xu and Junzhe Chen and Qiuyan Huang and Ya Liu and Tongtong Xu and Julie Wang and Nancy Olsen and Anping Xu and Zheng, {Song Guo}",

note = "Funding Information: This work was in part supported by grants from the National Natural Science Funds, China ( 81670641 , 81870481 , 81871224 , and 81671611 ) and the Guangzhou Science and Technology project ( 201707010111 ) (all to A.X.) and the project of the Jiangsu Provincial Natural Science Foundation ( BK20151152 ) (to Y.L.). Publisher Copyright: {\textcopyright} 2019 The Author(s)",

year = "2019",

month = nov,

day = "6",

doi = "10.1016/j.ymthe.2019.07.014",

language = "English (US)",

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T1 - CD8+CD103+ iTregs Inhibit Chronic Graft-versus-Host Disease with Lupus Nephritis by the Increased Expression of CD39

AU - Zhang, Xiao

AU - Ouyang, Xia

AU - Xu, Zhenjian

AU - Chen, Junzhe

AU - Huang, Qiuyan

AU - Liu, Ya

AU - Xu, Tongtong

AU - Wang, Julie

AU - Olsen, Nancy

AU - Xu, Anping

AU - Zheng, Song Guo

N1 - Funding Information: This work was in part supported by grants from the National Natural Science Funds, China ( 81670641 , 81870481 , 81871224 , and 81671611 ) and the Guangzhou Science and Technology project ( 201707010111 ) (all to A.X.) and the project of the Jiangsu Provincial Natural Science Foundation ( BK20151152 ) (to Y.L.). Publisher Copyright: © 2019 The Author(s)

PY - 2019/11/6

Y1 - 2019/11/6

N2 - Many patients with systemic lupus erythematosus (SLE) have lupus nephritis, one of the severe complications of SLE. We previously reported that CD8+CD103+ T regulatory cells induced ex vivo with transforming growth factor β (TGF-β) (iTregs) inhibited immune cells responses to ameliorate excessive autoimmune inflammation. However, the molecular mechanism(s) underlying the role of these CD8+ iTregs is still unclear. Here we identified that CD39, which is highly expressed on CD8+ iTregs, crucially contributes to the immunosuppressive role of the CD8+CD103+ iTregs. We showed that adoptive transfer of CD8+CD103+ iTregs significantly relieves the chronic graft-versus-host disease with lupus nephritis and CD39 inhibitor mostly abolished the functional activities of these CD8+ iTregs in vitro and in vivo. CD39+ cells sorted from CD8+CD103+ iTregs were more effective in treating lupus nephritis than CD39− partner cells in vivo. Furthermore, human CD8+ iTregs displayed increased CD103 and CD39 expressions, and CD39 was involved in the suppressive function of human CD8+ iTregs. Thus, our data implicated a crucial role of CD39 in CD8+CD103+ iTregs in treating lupus nephritis, and CD39 could be a new phenotypic biomarker for the identification of highly qualified CD8+ Tregs. This subpopulation may have therapeutic potential in patients with SLE nephritis and other autoimmune diseases.

AB - Many patients with systemic lupus erythematosus (SLE) have lupus nephritis, one of the severe complications of SLE. We previously reported that CD8+CD103+ T regulatory cells induced ex vivo with transforming growth factor β (TGF-β) (iTregs) inhibited immune cells responses to ameliorate excessive autoimmune inflammation. However, the molecular mechanism(s) underlying the role of these CD8+ iTregs is still unclear. Here we identified that CD39, which is highly expressed on CD8+ iTregs, crucially contributes to the immunosuppressive role of the CD8+CD103+ iTregs. We showed that adoptive transfer of CD8+CD103+ iTregs significantly relieves the chronic graft-versus-host disease with lupus nephritis and CD39 inhibitor mostly abolished the functional activities of these CD8+ iTregs in vitro and in vivo. CD39+ cells sorted from CD8+CD103+ iTregs were more effective in treating lupus nephritis than CD39− partner cells in vivo. Furthermore, human CD8+ iTregs displayed increased CD103 and CD39 expressions, and CD39 was involved in the suppressive function of human CD8+ iTregs. Thus, our data implicated a crucial role of CD39 in CD8+CD103+ iTregs in treating lupus nephritis, and CD39 could be a new phenotypic biomarker for the identification of highly qualified CD8+ Tregs. This subpopulation may have therapeutic potential in patients with SLE nephritis and other autoimmune diseases.

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SN - 1525-0016

VL - 27

SP - 1963

EP - 1973

JO - Molecular Therapy

JF - Molecular Therapy

IS - 11

ER -

CD8+CD103+ iTregs Inhibit Chronic Graft-versus-Host Disease with Lupus Nephritis by the Increased Expression of CD39

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