Limits...
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 regulatory populations in diabetic patients and healthy controls. The number of Tregs (CD4+CD25+CD127−) T cells (a), FoxP3high Tregs (CD4+CD25+ CD127−) T cells (b), CTLA4high Tregs (CD4+CD25+ CD127−FoxP3high) T cells (c) and FoxP3 MFI on Tregs (CD4+CD25+ CD127−) T cells (d). Representative dot plot analysis of Treg sub-populations (CD3+CD4+CD25+CD127−; CD3+CD4+CD25+CD127−FoxP3+; CD3+CD4+CD25+CD127−FoxP3+CTLA4+) (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. MFI mean fluorescence intensity
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig8: Circulating regulatory populations in diabetic patients and healthy controls. The number of Tregs (CD4+CD25+CD127−) T cells (a), FoxP3high Tregs (CD4+CD25+ CD127−) T cells (b), CTLA4high Tregs (CD4+CD25+ CD127−FoxP3high) T cells (c) and FoxP3 MFI on Tregs (CD4+CD25+ CD127−) T cells (d). Representative dot plot analysis of Treg sub-populations (CD3+CD4+CD25+CD127−; CD3+CD4+CD25+CD127−FoxP3+; CD3+CD4+CD25+CD127−FoxP3+CTLA4+) (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. MFI mean fluorescence intensity

Mentions: Aberrant inflammation is present in several autoimmune diseases with enhanced activity in e.g. rheumatoid arthritis as well as reduced activity in certain tumours [25]. Recently this was demonstrated to relate to a reduced presence and activity of regulatory lymphocytes in autoimmune diseases and inversely an augmented activity of regulatory cells in tumours. To determine if regulatory T cells were modulated in our T2D cohort and associated with CFR, flow cytometric analysis of various Treg sub-populations in the peripheral blood was performed using gating strategy from Figs. 1 and 8e.Fig. 8


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 regulatory populations in diabetic patients and healthy controls. The number of Tregs (CD4+CD25+CD127−) T cells (a), FoxP3high Tregs (CD4+CD25+ CD127−) T cells (b), CTLA4high Tregs (CD4+CD25+ CD127−FoxP3high) T cells (c) and FoxP3 MFI on Tregs (CD4+CD25+ CD127−) T cells (d). Representative dot plot analysis of Treg sub-populations (CD3+CD4+CD25+CD127−; CD3+CD4+CD25+CD127−FoxP3+; CD3+CD4+CD25+CD127−FoxP3+CTLA4+) (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. MFI mean fluorescence intensity
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig8: Circulating regulatory populations in diabetic patients and healthy controls. The number of Tregs (CD4+CD25+CD127−) T cells (a), FoxP3high Tregs (CD4+CD25+ CD127−) T cells (b), CTLA4high Tregs (CD4+CD25+ CD127−FoxP3high) T cells (c) and FoxP3 MFI on Tregs (CD4+CD25+ CD127−) T cells (d). Representative dot plot analysis of Treg sub-populations (CD3+CD4+CD25+CD127−; CD3+CD4+CD25+CD127−FoxP3+; CD3+CD4+CD25+CD127−FoxP3+CTLA4+) (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. MFI mean fluorescence intensity
Mentions: Aberrant inflammation is present in several autoimmune diseases with enhanced activity in e.g. rheumatoid arthritis as well as reduced activity in certain tumours [25]. Recently this was demonstrated to relate to a reduced presence and activity of regulatory lymphocytes in autoimmune diseases and inversely an augmented activity of regulatory cells in tumours. To determine if regulatory T cells were modulated in our T2D cohort and associated with CFR, flow cytometric analysis of various Treg sub-populations in the peripheral blood was performed using gating strategy from Figs. 1 and 8e.Fig. 8

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