Low-dose IL-2 expands CD4+ regulatory T cells with a suppressive function in vitro via the STAT5-dependent pathway in patients with chronic kidney diseases

Autor: Xueyong Liu, Wei Wang, Jianchun Zhang, Shaohua Wang, Yuanyuan Li, Yang Wang, Haichang Huang, Jinghua Li, Song Jiang, Youkang Zhang, Liping Li
Rok vydání: 2018
Předmět:
Male
lymphocytes
0301 basic medicine
030232 urology & nephrology
Cell Separation
lcsh:RC870-923
Critical Care and Intensive Care Medicine
T-Lymphocytes
Regulatory
0302 clinical medicine
Laboratory Study
Chronic kidney disease
STAT5 Transcription Factor
STAT5
Immunity
Cellular
biology
Low dose
Forkhead Transcription Factors
hemic and immune systems
Glomerulonephritis
General Medicine
Flow Cytometry
Recombinant Proteins
Up-Regulation
Nephrology
Female
medicine.symptom
signaling
Signal Transduction
Adult
chemical and pharmacologic phenomena
Inflammation
Young Adult
03 medical and health sciences
medicine
Humans
In patient
RNA
Messenger
Renal Insufficiency
Chronic
business.industry
Th1 Cells
lcsh:Diseases of the genitourinary system. Urology
medicine.disease
cytokines
In vitro
030104 developmental biology
Immunology
biology.protein
Interleukin-2
Th17 Cells
business
glomerulonephritis
Function (biology)
Kidney disease
Zdroj: Renal Failure, Vol 40, Iss 1, Pp 280-288 (2018)
Renal Failure
ISSN: 1525-6049
0886-022X
DOI: 10.1080/0886022x.2018.1456462
Popis: Background: Patients with chronic kidney disease (CKD) often have CD4+ regulatory T cells (Tregs) dysfunction and chronic inflammation. We aim to investigate the effect, function, and related mechanism of low-dose IL-2 on CD4+ regulatory T cells expansion in vitro from patients with CKD. Methods: A total of 148 newly diagnosed patients with CKD at Stage III and 35 healthy volunteer subjects were recruited into our studies. The number of peripheral Tregs in peripheral blood mononuclear cells isolated from CKD patients, which were characterized by FACS as CD4+CD25hi and CD4+CD25+FoxP3+. The effect of low-dose IL-2 on expansion of Tregs, and the suppressive function of expanded Tregs were also analyzed by FACS. The levels of FoxP3 mRNA were detected by qRT-PCR. The activation of IL-2 induced Stat5 and blocking experiments were assessed by Western Blotting and FACS. Results: We found that the frequency of peripheral Tregs from CKD patients was significantly lower than that in healthy volunteer subjects. We also showed that IL-2 selectively expanded CD4+CD25hi and CD4+CD25+FoxP3+ regulatory T cells, and also upregulated the expression of FoxP3 mRNA. Our in vitro studies demonstrated that expanded CD4+ regulatory T cells from CKD patients suppressed proinflammatory Th1 and Th17 cell response. Furthermore, STAT5 activation is required for IL-2-induced expansion of regulatory T cells and expression of FoxP3 mRNA from CKD patients. Conclusions: Our findings support the clinical Treg defects in CKD patients with glomerular diseases, and the rationale of evaluating low-dose IL-2 treatment for selectively modulating CD4+ Tregs.
Databáze: OpenAIRE
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