Your browser doesn't support javascript.
loading
Granzyme B + CD8 + T cells with terminal differentiated effector signature determine multiple sclerosis progression.
Shi, Ziyan; Wang, Xiaofei; Wang, Jiancheng; Chen, Hongxi; Du, Qin; Lang, Yanlin; Kong, Lingyao; Luo, Wenqin; Qiu, Yuhan; Zhang, Ying; Li, Chen; Wen, Dingke; Yao, Jie; Cheng, Xia; Cai, Linjun; Lin, Xue; Wang, Rui; Mou, Zichao; Li, Shuangjie; Liu, Duanya; Zhou, Hong; Zhou, Hongyu; Yang, Mu.
Afiliação
  • Shi Z; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Wang X; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Wang J; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Chen H; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Du Q; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Lang Y; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Kong L; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Luo W; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Qiu Y; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Zhang Y; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Li C; Centre for Translational Research in Cancer, Sichuan Cancer Hospital and Institute, No.55 South Renmin Road, Chengdu, 610000, China.
  • Wen D; School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, China.
  • Yao J; Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Cheng X; Centre for Translational Research in Cancer, Sichuan Cancer Hospital and Institute, No.55 South Renmin Road, Chengdu, 610000, China.
  • Cai L; Centre for Translational Research in Cancer, Sichuan Cancer Hospital and Institute, No.55 South Renmin Road, Chengdu, 610000, China.
  • Lin X; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Wang R; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Mou Z; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Li S; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Liu D; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China.
  • Zhou H; School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, China.
  • Zhou H; School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610000, China.
  • Yang M; Department of Neurology, West China Hospital, Sichuan University, No.28 Dianxin Nan Street, Chengdu, 610041, China. zhouhy@scu.edu.cn.
J Neuroinflammation ; 20(1): 138, 2023 Jun 02.
Article em En | MEDLINE | ID: mdl-37268957
ABSTRACT

BACKGROUND:

Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing-remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS.

METHODS:

Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively.

RESULTS:

Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed distinct trajectory from clonal expansion. In addition, T-bet acted as a key transcriptional factor that elicited GzmB expression in CD8 + TEMRA cells of patients with SPMS. Finally, the expression of GzmB in CD8 + T cells was positively correlated with disability and progression of MS, and could effectively distinguish SPMS from RRMS with a high accuracy.

CONCLUSIONS:

Our study mapped peripheral immune cells of RRMS and SPMS patients and provided an evidence for the involvement of GzmB + CD8 + TEMRA cells in the progression of MS, which could be used as a diagnostic biomarker for distinguishing SPMS from RRMS.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Múltipla Crônica Progressiva / Esclerose Múltipla Recidivante-Remitente / Esclerose Múltipla Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Múltipla Crônica Progressiva / Esclerose Múltipla Recidivante-Remitente / Esclerose Múltipla Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article