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

Total number of circulating monocyte populations in diabetic patients and healthy controls. Representative dot-plot and scatter-plots of CD14 vs CD16 and their expression of CD11c 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
getmorefigures.php?uid=PMC4837587&req=5

Fig3: Total number of circulating monocyte populations in diabetic patients and healthy controls. Representative dot-plot and scatter-plots of CD14 vs CD16 and their expression of CD11c 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: Low grade inflammation is characterized by an enhanced number of M1-like macrophages in adipose tissue and skeletal muscle. The total number of circulating monocytes is not significantly modulated in patients at risk to develop T2D [17], while pre-clinical models of T2D have demonstrated that the monocyte population undergoes a repolarization from an initial M1-like phenotype into a M2-like phenotype in established disease [18]. To address if patients with established T2D display an altered profile of circulating monocyte polarization profile compared to healthy subjects associated with CFR, we performed analysis of peripheral blood in our T2D patient cohort. Using the gating strategy in Additional file 1: Figure S1 and Fig. 3 monocyte subsets were identified.Fig. 3


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)

Total number of circulating monocyte populations in diabetic patients and healthy controls. Representative dot-plot and scatter-plots of CD14 vs CD16 and their expression of CD11c 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

Fig3: Total number of circulating monocyte populations in diabetic patients and healthy controls. Representative dot-plot and scatter-plots of CD14 vs CD16 and their expression of CD11c 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: Low grade inflammation is characterized by an enhanced number of M1-like macrophages in adipose tissue and skeletal muscle. The total number of circulating monocytes is not significantly modulated in patients at risk to develop T2D [17], while pre-clinical models of T2D have demonstrated that the monocyte population undergoes a repolarization from an initial M1-like phenotype into a M2-like phenotype in established disease [18]. To address if patients with established T2D display an altered profile of circulating monocyte polarization profile compared to healthy subjects associated with CFR, we performed analysis of peripheral blood in our T2D patient cohort. Using the gating strategy in Additional file 1: Figure S1 and Fig. 3 monocyte subsets were identified.Fig. 3

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