Identification and Characterization of CD8+ CD27+ CXCR3- T Cell Dysregulation and Progression-Associated Biomarkers in Systemic Lupus Erythematosus

Lulu Zhang; Fang Du; Qiqi Jin; Li Sun; Boqian Wang; Ziyang Tan; Xinyu Meng; Baozhen Huang; Yifan Zhan; Wenqiong Su; Rui Song; Chunmei Wu; Luonan Chen; Xiaoxiang Chen; Xianting Ding

doi:10.1002/advs.202300123

Identification and Characterization of CD8⁺ CD27⁺ CXCR3^- T Cell Dysregulation and Progression-Associated Biomarkers in Systemic Lupus Erythematosus

Adv Sci (Weinh). 2023 Dec;10(35):e2300123. doi: 10.1002/advs.202300123. Epub 2023 Oct 24.

Authors

Lulu Zhang^{1

2}, Fang Du^{1

2}, Qiqi Jin^{3

4

5}, Li Sun⁶, Boqian Wang^{1

2}, Ziyang Tan⁷, Xinyu Meng², Baozhen Huang⁸, Yifan Zhan⁹, Wenqiong Su², Rui Song^{1

10}, Chunmei Wu¹, Luonan Chen^{3

5

11}, Xiaoxiang Chen¹, Xianting Ding^{1

2}

Affiliations

¹ Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital and School of Biomedical Engineering, Shanghai, 200030, China.
² State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200001, China.
³ Key Laboratory of Systems Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China.
⁴ University of Chinese Academy of Sciences, Beijing, 100049, China.
⁵ School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
⁶ Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
⁷ Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Solna, 17121, Sweden.
⁸ Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 999077, China.
⁹ Drug Discovery, Shanghai Huaota Biopharmaceutical Co. Ltd., Shanghai, 200131, China.
¹⁰ Nantong First People's Hospital, Affiliated Hospital 2 of Nantong University, Nantong Hospital of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.
¹¹ Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, 310024, China.

Abstract

Systemic Lupus Erythematosus (SLE) etiopathogenesis highlights the contributions of overproduction of CD4⁺ T cells and loss of immune tolerance. However, the involvement of CD8⁺ T cells in SLE pathology and disease progression remains unclear. Here, the comprehensive immune cell dysregulation in total 263 clinical peripheral blood samples composed of active SLE (aSLE), remission SLE (rSLE) and healthy controls (HCs) is investigated via mass cytometry, flow cytometry and single-cell RNA sequencing. This is observed that CD8⁺ CD27⁺ CXCR3^- T cells are increased in rSLE compare to aSLE. Meanwhile, the effector function of CD8⁺ CD27⁺ CXCR3^- T cells are overactive in aSLE compare to HCs and rSLE, and are positively associated with clinical SLE activity. In addition, the response of peripheral blood mononuclear cells (PBMCs) is monitored to interleukin-2 stimulation in aSLE and rSLE to construct dynamic network biomarker (DNB) model. It is demonstrated that DNB score-related parameters can faithfully predict the remission of aSLE and the flares of rSLE. The abundance and functional dysregulation of CD8⁺ CD27⁺ CXCR3^- T cells can be potential biomarkers for SLE prognosis and concomitant diagnosis. The DNB score with accurate prediction to SLE disease progression can provide clinical treatment suggestions especially for drug dosage determination.

Keywords: dynamic network biomarker; mass cytometry; single-cell RNA sequencing; systemic lupus erythematosus.

MeSH terms

Biomarkers
CD4-Positive T-Lymphocytes*
CD8-Positive T-Lymphocytes
Disease Progression
Humans
Leukocytes, Mononuclear
Lupus Erythematosus, Systemic* / diagnosis
Receptors, CXCR3

Substances

Biomarkers
CXCR3 protein, human
Receptors, CXCR3

Abstract

MeSH terms

Substances

Grants and funding