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Scand J Immunol. 2018 Oct;88(4):e12711. doi: 10.1111/sji.12711.

Decreased regulatory function of CD4+CD25+CD45RA+ T cells and impaired IL-2 signalling pathway in patients with type 2 diabetes mellitus.

Author information

1
Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
2
Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
3
Molecular Immunology Research Group, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
4
Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
5
Inflammation and Inflammatory Diseases Division, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

In this study, the frequency and function of CD4+CD25+CD45RA+ regulatory T cells (Treg) and intracellular IL-2 signalling molecules in patients with type 2 diabetes mellitus (T2DM) were investigated. Tregs and responder T cells (Tresp, CD4+CD25- T cells) were sorted and suppression assays were performed using flow cytometry. Phosphorylation of signal transducer and activator of transcription-5 (pSTAT5) were assessed using flow cytometry. Gene expression of FOXP3 was performed with the SYBR green Real Time PCR method. Production of IL-2 from cultured cells was assessed using ELISA. We observed a functional defect of CD4+CD25+CD45RA+ Tregs in T2DM patients with higher proliferation of Tresp cells, in response to anti-CD3 and anti CD28 stimulation in the presence of Tregs in vitro. The results showed that the proliferation of Tresps in the absence of Treg cells was higher in T2DM patients than in healthy controls. Decreased FOXP3 mRNA expression and pSTAT5 were observed within the Tregs of the patients, whereas the level of secreted IL-2 from PBMCs culture was not statically different between T2DM patients and healthy individuals. Changes in intracellular IL-2 pathways and FOXP3 gene expression may contribute to the defect of Tregs in T2DM patients. These findings indicating that the purified CD4+CD25+CD45RA+ Treg cells have reduced functional capacity together with impaired IL-2 pathway in T2DM, and the Tregs could be used for a potential novel therapeutic target.

KEYWORDS:

FOXP3; IL‐2; STAT5; T2DM; Treg

PMID:
30270447
DOI:
10.1111/sji.12711
[Indexed for MEDLINE]

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