Coordinated Priming of NKG2D Pathway by IL-15 Enhanced Functional Properties of Cytotoxic CD4(+)CD28(-) T Cells Expanded in Systemic Lupus Erythematosus

Wang, Tingting1,2; Wei, Laiyou3,4; Meng, Shuhui1; Song, Wencong1; Chen, Yulan1; Li, Heng1,2; Zhao, Qianqian1,2; Jiang, Zhenyou5; Liu, Dongzhou1,3,4; Ren, Huan1,3; Hong, Xiaoping1,3,4

2023-07-01

10.1007/s10753-023-01860-z

INFLAMMATION   影响因子和分区

0360-3997

1573-2576

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder, and numerous aberrations of T cell responses have been reported and were implicated in its pathophysiology. Recently, CD4-positive T cells with cytotoxic potential were shown to be involved in autoimmune disease progression and tissue damage. However, the effector functions of this cell type and their potential molecular mechanisms in SLE patients remain to be elucidated. In this study, we find that cytotoxic CD4(+)CD28(-) T cells are expanded in SLE patients with flow cytometry analysis, and the percentage of CD4(+)CD28(-) T cells positively correlates with the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI). Furthermore, our study suggests that interleukin-15 (IL-15) promotes the expansion, proliferation, and cytotoxic function of CD4(+)CD28(-) T cells in SLE patients through activation of the Janus kinase3-STAT5 pathway. Further study indicates that IL-15 not only mediates the upregulation of NKG2D, but also cooperates with the NKG2D pathway to regulate the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Together, our study demonstrated that proinflammatory and cytolytic CD4(+)CD28(-) T cells expand in SLE patients. The pathogenic potential of these CD4(+)CD28(-) T cells is driven by the coupling of the IL-15/IL-15R signaling pathway and the NKG2D/DAP10 signaling pathway, which may open new avenues for therapeutic intervention to prevent SLE progression.

interleukin-15-NKG2D cytotoxic CD4(+)CD28(-) T cells inflammation cytolytic function tissue damage

SCI

英语

通讯

National Natural Science Foundation of China["82201996","JCYJ20220530151811025"] ; Guangdong Basic and Applied Basic Research Fund[81971464] ; Science and innovation commission of Shenzhen municipality[2021A1515111072]

Cell Biology ; Immunology

Cell Biology ; Immunology

WOS:001024871500001

SPRINGER/PLENUM PUBLISHERS

IMMUNOLOGY

Web of Science

1.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Rheumatol & Immunol, Shenzhen 518020, Peoples R China
2.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou 510632, Peoples R China
3.Southern Univ Sci & Technol, Sch Med, Shenzhen 518055, Angola
4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen 518020, Peoples R China
5.Jinan Univ, Coll Basic Med & Publ Hyg, Dept Microbiol & Immunol, Guangzhou 510632, Peoples R China

Wang, Tingting,Wei, Laiyou,Meng, Shuhui,et al. Coordinated Priming of NKG2D Pathway by IL-15 Enhanced Functional Properties of Cytotoxic CD4(+)CD28(-) T Cells Expanded in Systemic Lupus Erythematosus[J]. INFLAMMATION,2023,46(5).

Wang, Tingting.,Wei, Laiyou.,Meng, Shuhui.,Song, Wencong.,Chen, Yulan.,...&Hong, Xiaoping.(2023).Coordinated Priming of NKG2D Pathway by IL-15 Enhanced Functional Properties of Cytotoxic CD4(+)CD28(-) T Cells Expanded in Systemic Lupus Erythematosus.INFLAMMATION,46(5).

Wang, Tingting,et al."Coordinated Priming of NKG2D Pathway by IL-15 Enhanced Functional Properties of Cytotoxic CD4(+)CD28(-) T Cells Expanded in Systemic Lupus Erythematosus".INFLAMMATION 46.5(2023).