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Impaired coronary microcirculation in type 2 diabetic patients is associated with elevated circulating regulatory T cells and reduced number of IL-21R⁺ T cells.

von Scholten BJ, Rosendahl A, Hasbak P, Bergholdt R, Kjaer A, Rossing P, Hansen TW - Cardiovasc Diabetol (2016)

Bottom Line: Presence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression.Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR.In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.

View Article: PubMed Central - PubMed

Affiliation: Department of Diabetic Complications, Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark. bjos@steno.dk.

ABSTRACT

Background: Low-grade systemic inflammation is considered to participate in the progression of type 2 diabetes (T2D) and in diabetic complications.

Methods: To determine if circulating leukocytes were abnormally regulated in T2D patients, 8-color flow-cytometry (FACS) analysis was performed in a cross-sectional study of 37 T2D patients and 16 controls. Data obtained from the FACS analysis were compared to coronary flow reserve (CFR), assessed by Rb(82)-PET-imaging, to uncover inflammatory signatures associated with impaired CFR.

Results: Presence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression. Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR. In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.

Conclusions: Our demonstration that HbA1c inversely correlates to several T cell populations suggests that T cells may play disease modulating roles in T2D. Further, the novel association between impaired CFR and regulatory T cells and IL-21R(+) T cells imply an intricate balance in maintaining tissue homeostasis in vascular diabetic complications.

No MeSH data available.


Related in: MedlinePlus

TLR4 expression level on leukocyte populations in diabetic patients and healthy controls. The TLR4 expression on CD4+ T cells (a), CD8+ T cells (b), B cells (c) and CD68+ monocytes (d) is shown. Representative dot plot analysis of TLR4 expression on CD19, CD68, CD4 and CD8+ cells (e) that were first identified using the gating strategy from Figs. 1, 2 and Additional file 1: Figure S1. A total of 2 ml blood was analysed and the total number of each cell population was calculated as described in the “Methods” section. Each dot represents one individual and the horizontal line represents the mean value in each group. P values represent difference between groups assessed by t test
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Fig7: TLR4 expression level on leukocyte populations in diabetic patients and healthy controls. The TLR4 expression on CD4+ T cells (a), CD8+ T cells (b), B cells (c) and CD68+ monocytes (d) is shown. Representative dot plot analysis of TLR4 expression on CD19, CD68, CD4 and CD8+ cells (e) that were first identified using the gating strategy from Figs. 1, 2 and Additional file 1: Figure S1. A total of 2 ml blood was analysed and the total number of each cell population was calculated as described in the “Methods” section. Each dot represents one individual and the horizontal line represents the mean value in each group. P values represent difference between groups assessed by t test

Mentions: TLR4 expression on B cells and T cells has been associated with immunosuppressive effect [22, 23]. Further, TLR4 expressing B cells are associated with increasing body mass index and an inverse correlation exists between the number of TLR4 T cells and fasting plasma glucose in pre-diabetic as risk [24]. To determine if TLR4 expression level is modulated in patients with T2D and associated with CFR, we performed flow cytometric analysis of the blood in our T2D cohort using the gating strategy from Additional file 1: Figure S1 and Fig. 7e.Fig. 7


Impaired coronary microcirculation in type 2 diabetic patients is associated with elevated circulating regulatory T cells and reduced number of IL-21R⁺ T cells.

von Scholten BJ, Rosendahl A, Hasbak P, Bergholdt R, Kjaer A, Rossing P, Hansen TW - Cardiovasc Diabetol (2016)

TLR4 expression level on leukocyte populations in diabetic patients and healthy controls. The TLR4 expression on CD4+ T cells (a), CD8+ T cells (b), B cells (c) and CD68+ monocytes (d) is shown. Representative dot plot analysis of TLR4 expression on CD19, CD68, CD4 and CD8+ cells (e) that were first identified using the gating strategy from Figs. 1, 2 and Additional file 1: Figure S1. A total of 2 ml blood was analysed and the total number of each cell population was calculated as described in the “Methods” section. Each dot represents one individual and the horizontal line represents the mean value in each group. P values represent difference between groups assessed by t test
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4837587&req=5

Fig7: TLR4 expression level on leukocyte populations in diabetic patients and healthy controls. The TLR4 expression on CD4+ T cells (a), CD8+ T cells (b), B cells (c) and CD68+ monocytes (d) is shown. Representative dot plot analysis of TLR4 expression on CD19, CD68, CD4 and CD8+ cells (e) that were first identified using the gating strategy from Figs. 1, 2 and Additional file 1: Figure S1. A total of 2 ml blood was analysed and the total number of each cell population was calculated as described in the “Methods” section. Each dot represents one individual and the horizontal line represents the mean value in each group. P values represent difference between groups assessed by t test
Mentions: TLR4 expression on B cells and T cells has been associated with immunosuppressive effect [22, 23]. Further, TLR4 expressing B cells are associated with increasing body mass index and an inverse correlation exists between the number of TLR4 T cells and fasting plasma glucose in pre-diabetic as risk [24]. To determine if TLR4 expression level is modulated in patients with T2D and associated with CFR, we performed flow cytometric analysis of the blood in our T2D cohort using the gating strategy from Additional file 1: Figure S1 and Fig. 7e.Fig. 7

Bottom Line: Presence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression.Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR.In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.

View Article: PubMed Central - PubMed

Affiliation: Department of Diabetic Complications, Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark. bjos@steno.dk.

ABSTRACT

Background: Low-grade systemic inflammation is considered to participate in the progression of type 2 diabetes (T2D) and in diabetic complications.

Methods: To determine if circulating leukocytes were abnormally regulated in T2D patients, 8-color flow-cytometry (FACS) analysis was performed in a cross-sectional study of 37 T2D patients and 16 controls. Data obtained from the FACS analysis were compared to coronary flow reserve (CFR), assessed by Rb(82)-PET-imaging, to uncover inflammatory signatures associated with impaired CFR.

Results: Presence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression. Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR. In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.

Conclusions: Our demonstration that HbA1c inversely correlates to several T cell populations suggests that T cells may play disease modulating roles in T2D. Further, the novel association between impaired CFR and regulatory T cells and IL-21R(+) T cells imply an intricate balance in maintaining tissue homeostasis in vascular diabetic complications.

No MeSH data available.


Related in: MedlinePlus