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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

Circulating lymphocyte populations in diabetic patients and healthy controls. A representative gating strategy for T cell subsets is shown after first identifying the cells using gating strategy in 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
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Fig1: Circulating lymphocyte populations in diabetic patients and healthy controls. A representative gating strategy for T cell subsets is shown after first identifying the cells using gating strategy in 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

Mentions: The total number of circulating whole blood cells is known to be increased in obese subjects [16]. Detailed analysis in T2D patients is yet to be carefully evaluated and linked to risk parameters. Hence, we determined if the number of T and B cells was modulated in our T2D patient cohort using the gating strategy shown in Additional file 1: Figure S1 and Fig. 1.Fig. 1


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)

Circulating lymphocyte populations in diabetic patients and healthy controls. A representative gating strategy for T cell subsets is shown after first identifying the cells using gating strategy in 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
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Circulating lymphocyte populations in diabetic patients and healthy controls. A representative gating strategy for T cell subsets is shown after first identifying the cells using gating strategy in 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
Mentions: The total number of circulating whole blood cells is known to be increased in obese subjects [16]. Detailed analysis in T2D patients is yet to be carefully evaluated and linked to risk parameters. Hence, we determined if the number of T and B cells was modulated in our T2D patient cohort using the gating strategy shown in Additional file 1: Figure S1 and Fig. 1.Fig. 1

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