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Magnusson, L., Barcenilla, H., Pihl, M., Bensing, S., Espes, D., Carlsson, P.-O. & Casas, R. (2020). Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets. Frontiers in Immunology, 11, Article ID 288.
Open this publication in new window or tab >>Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets
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2020 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 11, article id 288Article in journal (Refereed) Published
Abstract [en]

Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45(+) cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease and autoimmune Addison's disease (AD), as well as healthy controls. The frequency of CD20(lo)CD27(hi)CD38(hi)HLA-DRint plasmablasts, CD86(+)CD14(lo)CD16(+) non-classical monocytes and two subsets of CD56(dim)HLA-DR+IFN-gamma(+) NK cells were increased in patients with HT. Subsets of CD56(dim)CD69(+)HLA-DR- NK cells and CD8(+) TEMRA cells, both expressing IFN-gamma, were expanded and reduced, respectively, in the N-T1D group. In addition, patients with AD were characterized by an increased percentage of central memory CD8(+) T cells that expressed CCR4, GATA3, and IL-2. We demonstrate that patients with N-T1D, HT, and AD had altered frequencies of distinct subsets within antigen-presenting and cytotoxic cell lineages. Previously unreported alterations of specific cell subsets were identified in samples from patients with HT and AD. Our study might contribute to a better understanding of shared and diverging immunological features between autoimmune endocrine diseases.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2020
Keywords
mass cytometry (CyTOF), type 1 diabetes, Hashimoto's thyroiditis, Graves' disease, Addison's disease, antigen-presenting cells, NK cells, T cells
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-409928 (URN)10.3389/fimmu.2020.00288 (DOI)000523747500001 ()32153591 (PubMedID)
Funder
Swedish Research Council, 2017-01343Swedish Research Council, 2014-07054Swedish Diabetes AssociationSwedish Child Diabetes FoundationNovo Nordisk
Available from: 2020-05-11 Created: 2020-05-11 Last updated: 2020-05-11Bibliographically approved
Katsogiannos, P., Kamble, P. G., Wiklund, U., Sundbom, M., Espes, D., Hammar, U., . . . Eriksson, J. (2020). Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery. Endocrine (Basingstoke), 67(2), 344-353
Open this publication in new window or tab >>Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery
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2020 (English)In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 67, no 2, p. 344-353Article in journal (Refereed) Published
Abstract [en]

Objective: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB).

Research design and methods: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed.

Results: At both 4 and 24 weeks post-RYGB the following effects were found: arginine-stimulated insulin secretion was reduced. GLP-1, GIP, and glucagon rise during OGTT was enhanced. IGF-1 and GH levels increased. In addition, total HRV and spectral components P-LF (power of low frequency) and P-HF (power of high frequency) increased. At 4 weeks, morning cortisol was lower than baseline and 24 weeks. At 24 weeks, NEFA levels during OGTT, and the P-LF/P-HF ratio decreased. None of these changes were seen in the control group.

Conclusions: There were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.

Place, publisher, year, edition, pages
SPRINGER, 2020
Keywords
Roux-en-Y gastric bypass, Type 2 diabetes, Incretins, Adipokines, Heart rate variability
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-407498 (URN)10.1007/s12020-020-02203-w (DOI)000514540100009 ()31983031 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2020-03-26 Created: 2020-03-26 Last updated: 2020-03-26Bibliographically approved
Singh, K., Martinell, M., Luo, Z., Espes, D., Stålhammar, J., Sandler, S. & Carlsson, P.-O. (2019). Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes. Clinical and Experimental Immunology, 197(1), 64-73
Open this publication in new window or tab >>Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes
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2019 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 197, no 1, p. 64-73Article in journal (Refereed) Published
Abstract [en]

There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age-matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)-35 were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD11c(+)CD123(-) antigen-presenting cells (APCs) was lower, while the proportions of CD11c(+)CD123(+) APCs and IL-35(+) tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3(-)CD56(high)CD16(+) natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL-35(+) regulatory T cells and plasma IL-35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL-35(+) regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

Keywords
Cellular immunology, IL-35, LADA, type 1 diabetes, type 2 diabetes
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-393134 (URN)10.1111/cei.13289 (DOI)000480400100004 ()30843600 (PubMedID)
Funder
Swedish Research Council, 2017-01343Swedish Research Council, 921-2014-7054Swedish Diabetes AssociationSwedish Child Diabetes FoundationEXODIAB - Excellence of Diabetes Research in SwedenNovo Nordisk
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
Elksnis, A., Martinell, M., Eriksson, O. & Espes, D. (2019). Heterogeneity of Metabolic Defects in Type 2 Diabetes and Its Relation to Reactive Oxygen Species and Alterations in Beta-Cell Mass. Frontiers in Physiology, 10, Article ID 107.
Open this publication in new window or tab >>Heterogeneity of Metabolic Defects in Type 2 Diabetes and Its Relation to Reactive Oxygen Species and Alterations in Beta-Cell Mass
2019 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 107Article, review/survey (Refereed) Published
Abstract [en]

Type 2 diabetes (T2D) is a complex and heterogeneous disease which affects millions of people worldwide. The classification of diabetes is at an interesting turning point and there have been several recent reports on sub-classification of T2D based on phenotypical and metabolic characteristics. An important, and perhaps so far underestimated, factor in the pathophysiology of T2D is the role of oxidative stress and reactive oxygen species (ROS). There are multiple pathways for excessive ROS formation in T2D and in addition, beta-cells have an inherent deficit in the capacity to cope with oxidative stress. ROS formation could be causal, but also contribute to a large number of the metabolic defects in T2D, including beta-cell dysfunction and loss. Currently, our knowledge on beta-cell mass is limited to autopsy studies and based on comparisons with healthy controls. The combined evidence suggests that beta-cell mass is unaltered at onset of T2D but that it declines progressively. In order to better understand the pathophysiology of T2D, to identify and evaluate novel treatments, there is a need for in vivo techniques able to quantify beta-cell mass. Positron emission tomography holds great potential for this purpose and can in addition map metabolic defects, including ROS activity, in specific tissue compartments. In this review, we highlight the different phenotypical features of T2D and how metabolic defects impact oxidative stress and ROS formation. In addition, we review the literature on alterations of beta-cell mass in T2D and discuss potential techniques to assess beta-cell mass and metabolic defects in vivo.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
type 2 diabetes, diabetes classification, oxygen stress, reactive oxygen species, beta-cell, beta-cell mass, imaging, positron emission tomography
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-378233 (URN)10.3389/fphys.2019.00107 (DOI)000458732800001 ()
Funder
Swedish Child Diabetes FoundationSwedish Society for Medical Research (SSMF)Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceErnfors FoundationSwedish Diabetes AssociationGöran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology
Available from: 2019-03-15 Created: 2019-03-15 Last updated: 2019-03-15Bibliographically approved
Eriksson, O., Selvaraju, R., Berglund, M. & Espes, D. (2019). Metabolically Active Brown Adipose Tissue Is Found in Adult Subjects with Type 1 Diabetes.. International Journal of Molecular Sciences, 20(23), Article ID E5827.
Open this publication in new window or tab >>Metabolically Active Brown Adipose Tissue Is Found in Adult Subjects with Type 1 Diabetes.
2019 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 23, article id E5827Article in journal (Refereed) Published
Abstract [en]

Type 1 diabetes (T1D) is characterized by the loss of insulin-producing cells and hence insulin secretion and metabolic control. In addition to insulin, there are a number of hormones and cytokines that influence metabolism, and many of these can be secreted from brown adipose tissue (BAT). However, the presence and activity of BAT in T1D have not been studied, despite the fact that preclinical studies have shown that transplantation of BAT in mouse models of T1D can restore metabolic control. The metabolic activity of BAT, white adipose tissue (WAT), and skeletal muscle was investigated in patients with T1D (n = 11) by 2-deoxy-2-(18F)fluoro-D-glucose PET/CT after cold stimulation. Functional BAT was detected in 4 out of 11 individuals with T1D with a prevalence of 36%. The glucose utilization rate in the supraclavicular BAT regions ranged from 0.75-38.7 µmol × min-1 × 100 g-1. The glucose utilization per gram tissue was higher in BAT when compared with both WAT (p = 0.049) and skeletal muscle (p = 0.039). However, no correlation between BAT activity and metabolic control or insulin requirements was found. In conclusion, for the first time, cold-induced BAT was detected in patients with T1D with a wide range in metabolic activity. Contrary to findings in animal models, the metabolic activity of BAT had negligible impact on insulin requirements or metabolic control in T1D under normal physiological conditions.

Keywords
brown adipose tissue, metabolic control, positron emission tomography, type 1 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-399124 (URN)10.3390/ijms20235827 (DOI)000504428300009 ()31757005 (PubMedID)
Funder
Magnus Bergvall FoundationFredrik och Ingrid Thurings StiftelseScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceEXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-12-12 Created: 2019-12-12 Last updated: 2020-01-22Bibliographically approved
Espes, D., Manell, E., Rydén, A., Carlbom, L., Weis, J., Jensen-Waern, M., . . . Eriksson, O. (2019). Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI. Acta Diabetologica, 56(10), 1113-1120
Open this publication in new window or tab >>Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI
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2019 (English)In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 56, no 10, p. 1113-1120Article in journal (Refereed) Published
Abstract [en]

AIMS: Perfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique.

METHODS: Pigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose.

RESULTS: Pancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p < 0.01). The absolute quantification of pancreatic perfusion (ml/min/g) by [15O]H2O PET was within a 15% error of margin of the microsphere technique.

CONCLUSION: Pancreatic perfusion by [15O]H2O PET was in agreement with the microsphere technique assessment. The IVIM MRI method has the potential to replace [15O]H2O PET if the pancreatic perfusion is sufficiently large, but not when absolute quantitation is required.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Diabetes, Hybrid scanner, PET/MRI scanner, Pancreas perfusion
National Category
Endocrinology and Diabetes Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-383433 (URN)10.1007/s00592-019-01353-2 (DOI)000486160600003 ()31028528 (PubMedID)
Funder
Ernfors FoundationGöran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologySwedish Diabetes AssociationSwedish Child Diabetes FoundationEXODIAB - Excellence of Diabetes Research in SwedenScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2019-05-14 Created: 2019-05-14 Last updated: 2019-10-31Bibliographically approved
Liljebäck, H., Espes, D. & Carlsson, P.-O. (2019). Unsurpassed Intrahepatic Islet Engraftment: the Quest for New Sites for Beta Cell Replacement. Cell Medicine, 11, Article ID 2155179019857662.
Open this publication in new window or tab >>Unsurpassed Intrahepatic Islet Engraftment: the Quest for New Sites for Beta Cell Replacement
2019 (English)In: Cell Medicine, ISSN 2155-1790, E-ISSN 2155-1790, Vol. 11, article id 2155179019857662Article in journal, Editorial material (Other academic) Published
Abstract [en]

The liver is currently the site of choice for clinical islet transplantation, even though many alternative implantation sites have lately been proposed as more ideal for graft survival. The suggested sites, for example intramuscular space, omentum, bone marrow, and spleen, are sometimes difficult to compare due to differences in animal model, islet isolation procedure, and islet quality. In addition, the variation in transplanted islet mass is vast. The aim of this commentary is to review alternative implantation sites tested experimentally as well as in clinical islet transplantation. Although many sites have been investigated, none have convincingly proved better suited for clinical islet transplantation than intraportal injection to the liver, regardless of whether it is autologous or allogeneic transplantation. However, in order to fully evaluate upcoming bioengineering techniques, such as scaffolds containing insulin-producing cells derived from stem cells, the need of an alternative site has arisen to enable cellular monitoring, which currently cannot be achieved within the liver.

Place, publisher, year, edition, pages
Sage Publications, 2019
Keywords
intraportal islet transplantation, type 1 diabetes, beta cell replacement
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-390334 (URN)10.1177/2155179019857662 (DOI)000472913100001 ()
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Bhandage, A., Jin, Z., Korol, S. V., Tafreshiha, A., Gohel, P., Hellgren, C., . . . Birnir, B. (2018). Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes. PLoS ONE, 13(12), Article ID e0208981.
Open this publication in new window or tab >>Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0208981Article in journal (Refereed) Published
Abstract [en]

Calcium (Ca2+) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca2+ has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca2+ can enter the cytoplasm either from intracellular stores or from outside the cells when Ca2+ permeable ion channels in the plasma membrane open. The Ca2+ release-activated (CRAC) channel is the most prominent Ca2+ ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca2+ sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca-2(+) channels in the plasma membrane are the voltage-gated Ca2+ (Ca-V) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and Ca-V gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca2+ channels was detected in the PBMCs where the Ca(V)2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the Ca(V)2.1 and Ca(V)3.2 genes were up-regulated only in pregnancy and the Ca(V)1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and Ca-V genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.

National Category
Endocrinology and Diabetes Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-372929 (URN)10.1371/journal.pone.0208981 (DOI)000453247500057 ()30543678 (PubMedID)
Funder
Swedish Research CouncilEXODIAB - Excellence of Diabetes Research in SwedenSwedish Diabetes AssociationSwedish Child Diabetes FoundationErnfors Foundation
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved
Korol, S. V., Jin, Z., Jin, Y., Bhandage, A. K., Tengholm, A., Gandasi, N. R., . . . Birnir, B. (2018). Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells. EBioMedicine, 30
Open this publication in new window or tab >>Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 30Article in journal (Refereed) Published
Abstract [en]

In human pancreatic islets, the neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule synthesized by and released from the insulin-secreting β cells. The effective, physiological GABA concentration range within human islets is unknown. Here we use native GABAA receptors in human islet β cells as biological sensors and reveal that 100-1000nM GABA elicit the maximal opening frequency of the single-channels. In saturating GABA, the channels desensitized and stopped working. GABA modulated insulin exocytosis and glucose-stimulated insulin secretion. GABAA receptor currents were enhanced by the benzodiazepine diazepam, the anesthetic propofol and the incretin glucagon-like peptide-1 (GLP-1) but not affected by the hypnotic zolpidem. In type 2 diabetes (T2D) islets, single-channel analysis revealed higher GABA affinity of the receptors. The findings reveal unique GABAA receptors signaling in human islets β cells that is GABA concentration-dependent, differentially regulated by drugs, modulates insulin secretion and is altered in T2D.

Keywords
GABA, GABA(A) receptor, Pancreatic islet, Type 2 diabetes
National Category
Other Medical Sciences not elsewhere specified Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-348267 (URN)10.1016/j.ebiom.2018.03.014 (DOI)000430303000032 ()29606630 (PubMedID)
Funder
Swedish Research Council, 521-2009-4021EXODIAB - Excellence of Diabetes Research in SwedenSwedish Child Diabetes FoundationSwedish Diabetes AssociationNovo NordiskSwedish Society for Medical Research (SSMF)Swedish Research Council, 521-2012-1789Swedish Research Council, 2015-02417Swedish Research Council, 2017-00956Swedish Research Council, 2014-2575
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-06-19Bibliographically approved
Bhandage, A. K., Jin, Z., Korol, S. V., Shen, Q., Pei, Y., Deng, Q., . . . Birnir, B. (2018). GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes. EBioMedicine, 30, 283-294
Open this publication in new window or tab >>GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 30, p. 283-294Article in journal (Refereed) Published
Abstract [en]

The neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule in the brain and in pancreatic islets. Here, we demonstrate that GABA regulates cytokine secretion from human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells. In anti-CD3 stimulated PBMCs, GABA (100nM) inhibited release of 47 cytokines in cells from patients with type 1 diabetes (T1D), but only 16 cytokines in cells from nondiabetic (ND) individuals. CD4+ T cells from ND individuals were grouped into responder or non-responder T cells according to effects of GABA (100nM, 500nM) on the cell proliferation. In the responder T cells, GABA decreased proliferation, and inhibited secretion of 37 cytokines in a concentration-dependent manner. In the non-responder T cells, GABA modulated release of 8 cytokines. GABA concentrations in plasma from T1D patients and ND individuals were correlated with 10 cytokines where 7 were increased in plasma of T1D patients. GABA inhibited secretion of 5 of these cytokines from both T1D PBMCs and ND responder T cells. The results identify GABA as a potent regulator of both Th1- and Th2-type cytokine secretion from human PBMCs and CD4+ T cells where GABA generally decreases the secretion.

Keywords
PBMCs, Immune cells, Proliferation, Cytokine, GABAA receptor, Diabetes, T1D, Autoimmune disease, T cell
National Category
Other Medical Sciences not elsewhere specified Endocrinology and Diabetes
Research subject
Biology; Physiology
Identifiers
urn:nbn:se:uu:diva-348232 (URN)10.1016/j.ebiom.2018.03.019 (DOI)000430303000033 ()
Funder
Swedish Research Council, 2015-02417Swedish Diabetes AssociationSwedish Child Diabetes FoundationEXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-06-19Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8843-7941

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