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

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.

Immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in the pathogenesis of chronic osteomyelitis

“…This may elevate the immunosuppressive activity of Treg cells, and compromise the immune response of T lymphocytes to pathogen. Thus, IL-2 mediated regulation of CD4+CD25+Foxp3 Treg cells via STAT5 pathway may play a key role in the development of COM (2)(3)(4)(5). To date, little is known about the role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in the pathogenesis of COM.…”

“…However, in control group, the bone tissues were closely arrangement, and there was no obvious bone destruction and infiltration of inflammatory cells in the medullary cavity (17). A variety of studies have shown the expression of IL-2 in the serum increases in patients with COM and COM animals (2)(3)(4)(5). Therefore, at different time points, the blood was collected for the detection of serum IL-2 concentration.…”

Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphisms

“…It has been suggested that there is a reduced immunosuppressive function of Tregs due to impaired IL-2 signalling in T1D (24-28), a defect which may subsequently lead to a more aggressive immune destruction of pancreatic b cells by T EFF (12,28). In addition, defects in the intracellular IL-2 pathways and a decreased regulatory function have recently been reported in patients with type 2 diabetes (T2D) (29). In many autoimmune diseases, such as multiple sclerosis (MS) (30), rheumatoid arthritis (31), primary Sjögren's syndrome (32), scleroderma (33), and inflammatory myopathies (34), but also in various cancers (31), sIL-2R has been proposed to be a biomarker for disease activity.…”

Effect of sitagliptin on serum levels of TNF-α, IL-1β and IL-10 in patients with type 2 diabetes mellitus

“…Zahra Telikani (M.Sc) 1,2 , Vida Sheikh (M.D) 3 , Alireza Zamani (Ph.D) 1,2 , Shiva Borzouei (M.D) 3 , Iraj Salehi (Ph.D) 4 , Mohammad Ali Amirzargar (M.D) 3 , Mahdi Alahgholi-Hajibehzad (Ph.D) *1,2 Introduction: Type 2 diabetes mellitus (T2DM) is an inflammatory disease with alterations in immune system. Remarkably, cytokine imbalance plays an important role in pathogenesis of T2DM.…”