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https://www.readbyqxmd.com/read/28081217/collective-genetic-interaction-effects-and-the-role-of-antigen-presenting-cells-in-autoimmune-diseases
#1
Hyung Jun Woo, Chenggang Yu, Jaques Reifman
Autoimmune diseases occur when immune cells fail to develop or lose their tolerance toward self and destroy body's own tissues. Both insufficient negative selection of self-reactive T cells and impaired development of regulatory T cells preventing effector cell activation are believed to contribute to autoimmunity. Genetic predispositions center around the major histocompatibility complex (MHC) class II loci involved in antigen presentation, the key determinant of CD4+ T cell activation. Recent studies suggested that variants in the MHC region also exhibit significant non-additive interaction effects...
2017: PloS One
https://www.readbyqxmd.com/read/28081180/pi3k%C3%AE-deficient-nod-mice-are-protected-from-diabetes-by-restoring-the-balance-of-regulatory-to-effector-t-cells
#2
Jamil Azzi, Lindsay Thueson, Robert Moore, Rozita Abdoli, Helena Reijonen, Reza Abdi
With a steady increase in its incidence and lack of curative treatment, type 1 diabetes (T1D) has emerged as a major health problem worldwide. To design novel effective therapies, there is a pressing need to identify regulatory targets controlling the balance of autoreactive to regulatory-T-cells (Tregs). We previously showed that the inhibition of the γ-subunit of the Phosphoinositide-3-kinase (PI3K), significantly suppress autoimmune-diabetes. To further delineate the mechanisms and the selectivity of specific immune modulation by PI3Kγ-inhibition, we developed a new NOD mouse model of T1D lacking the γ-subunit of PI3K...
2017: PloS One
https://www.readbyqxmd.com/read/28074676/potential-route-of-th17-treg-cell-dynamics-in-targeting-type-1-diabetes-and-rheumatoid-arthritis-an-autoimmune-disorder-perspective
#3
Suresh Kumar Karri, A Sheela
Cytokines, small secreted proteins, have a specific effect on the interactions and communications between cells. They play a pivotal role in the pathogenesis of autoimmune diseases. Factors in the breakdown of self-tolerance and the subsequent events leading to the induction of pathogenic responses remain unclear for most of the autoimmune diseases. Large numbers of studies have revealed a general scheme in which pro-inflammatory cytokines contribute to the initiation and propagation of autoimmune inflammation, whereas anti-inflammatory cytokines facilitate the regression of inflammation and thereby recovery from the disease...
January 11, 2017: British Journal of Biomedical Science
https://www.readbyqxmd.com/read/28065853/sitagliptin-inhibit-human-lymphocytes-proliferation-and-th1-th17-differentiation-in-vitro
#4
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
January 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28062695/the-clonal-invariant-nkt-cell-repertoire-in-people-with-type-1-diabetes-is-characterized-by-a-loss-of-clones-expressing-high-affinity-tcrs
#5
Anna S Tocheva, Salah Mansour, Tristan G H Holt, Samuel Jones, Andrew Chancellor, Joseph P Sanderson, Efrem Eren, Tim J Elliott, Richard I G Holt, Stephan D Gadola
Invariant NKT (iNKT) cells in healthy people express iNKT-TCRs with widely varying affinities for CD1d, suggesting different roles for high- and low-affinity iNKT clones in immune regulation. However, the functional implications of this heterogeneity have not yet been determined. Functionally aberrant iNKT responses have been previously demonstrated in different autoimmune diseases, including human type 1 diabetes, but their relationship to changes in the iNKT clonal repertoire have not been addressed. In this study, we directly compared the clonal iNKT repertoire of people with recent onset type 1 diabetes and age- and gender-matched healthy controls with regard to iNKT-TCR affinity and cytokine production...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28053319/pre-diagnostic-genotyping-identifies-t1d-subjects-with-impaired-treg-il-2-signaling-and-an-elevated-proportion-of-foxp3-il-17-cells
#6
A K Marwaha, C Panagiotopoulos, C M Biggs, S Staiger, K L Del Bel, A F Hirschfeld, J J Priatel, S E Turvey, R Tan
T-regulatory cells (Tregs) are essential for immune tolerance, and animal studies implicate their dysfunction in type 1 diabetes (T1D) pathogenesis. Tregs require interleukin-2 (IL-2) for their suppressive function, and variants in IL-2/IL-2R pathway genes have been associated with T1D. We previously reported that recent-onset T1D subjects have an increased population of FOXP3(lo) Tregs that secrete the pro-inflammatory cytokine, interleukin-17 (IL-17). We hypothesize that IL-2 signaling defects may drive T1D development by skewing protective Tregs towards an inflammatory Th17 phenotype...
January 5, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28045060/soluble-ox40l-and-jag1-induce-selective-proliferation-of-functional-regulatory-t-cells-independent-of-canonical-tcr-signaling
#7
Prabhakaran Kumar, Khaled Alharshawi, Palash Bhattacharya, Alejandra Marinelarena, Christine Haddad, Zuoming Sun, Shigeru Chiba, Alan L Epstein, Bellur S Prabhakar
Regulatory T-cells (Tregs) play a pivotal role in maintaining peripheral tolerance. Increasing Treg numbers/functions has been shown to ameliorate autoimmune diseases. However, common Treg expansion approaches use T-Cell Receptor (TCR)-mediated stimulation which also causes proliferation of effector T-cells (Teff). To overcome this limitation, purified patient-specific Tregs are expanded ex vivo and transfused. Although promising, this approach is not suitable for routine clinical use. Therefore, an alternative approach to selectively expand functional Tregs in vivo is highly desired...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28028935/renoprotection-focus-on-trpv1-trpv4-trpc6-and-trpm2
#8
REVIEW
L Markó, M Mannaa, T N Haschler, S Krämer, M Gollasch
Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca(2+) influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS)...
November 7, 2016: Acta Physiologica
https://www.readbyqxmd.com/read/28004148/an-enzymatically-stable-gip-xenin-hybrid-peptide-restores-gip-sensitivity-enhances-beta-cell-function-and-improves-glucose-homeostasis-in-high-fat-fed-mice
#9
Annie Hasib, Ming T Ng, Victor A Gault, Dawood Khan, Vadivel Parthsarathy, Peter R Flatt, Nigel Irwin
AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) and xenin, regulatory gut hormones secreted from enteroendocrine K cells, exert important effects on metabolism. In addition, xenin potentiates the biological actions of GIP. The present study assessed the actions and therapeutic utility of a (DAla(2))GIP/xenin-8-Gln hybrid peptide, in comparison with the parent peptides (DAla(2))GIP and xenin-8-Gln. METHODS: Following confirmation of enzymatic stability, insulin secretory activity of (DAla(2))GIP/xenin-8-Gln was assessed in BRIN-BD11 beta cells...
December 21, 2016: Diabetologia
https://www.readbyqxmd.com/read/27995404/circulating-zonulin-correlates-with-density-of-enteroviruses-and-tolerogenic-dendritic-cells-in-the-small-bowel-mucosa-of-celiac-disease-patients
#10
Tamara Vorobjova, Helerin Raikkerus, Lumme Kadaja, Ija Talja, Oivi Uibo, Kaire Heilman, Raivo Uibo
BACKGROUND: Impaired intestinal integrity, including increased permeability of the small bowel mucosa, has been shown in patients with celiac disease (CD) as well as with type 1 diabetes (T1D). Zonulin (ZO, pre-haptoglobin), a tight junction regulator, plays a particular role in the regulation of intestinal barrier function and in the pathogenesis of the above-mentioned diseases. AIM: To investigate whether enteroviruses (EVs) and immunoregulatory cells are associated with intestinal permeability in patients with CD alone and with coexistent T1D...
December 19, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27989874/effect-of-diabetea-tea-tm-consumption-on-inflammatory-cytokines-and-metabolic-biomarkers-in-type-2-diabetes-patients
#11
Fadia Mahmoud, Ebaa Al-Ozairi, David Haine, Ladislav Novotny, Ali Dashti, Basel Ibrahim, Mohamed Abdel-Hamid
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetea tea (TM) (DT) is an anti-diabetic alternative medicine in some Asian countries. The main constituent of DT is black tea originating from Camellia sinensis that is supplemented by 12 other medicinal plants. Black tea contains a large amount of the flavonoids catechins especially epigallocatechin gallate (EGCG) which has anti-inflammatory and antioxidative capacity. This study was undertaken to evaluate the possible effects of DT intake on inflammatory cytokines, regulatory T cells (Tregs) and metabolic biomarkers in T2DM...
October 27, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27939445/changes-in-adipose-tissue-cellular-composition-during-obesity-and-aging-as-a-cause-of-metabolic-dysregulation
#12
Kari Martyniak, Michal M Masternak
Adipose tissue represents complex endocrine organ containing several different cellular populations including adipocytes, pre-adipocytes, mesenchymal stem cells, macrophages and lymphocytes. It is well establishing that these populations are not static but alter during obesity and aging. Changes in cellular populations alter inflammatory status and other common metabolic complications arise, therefore adipose tissue cellular composition helps dictate its endocrine and regulatory function. During excessive weight gain in obese individuals and as we age there is shift towards increase populations of inflammatory macrophages with a decrease of regulatory T cell...
December 9, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27936460/b-cells-present-skewed-profile-and-lose-the-function-of-supporting-t-cell-inflammation-after-roux-en-y-gastric-bypass
#13
Xiaojiang Dai, Weiguo Zhao, Junfang Zhan, Songhua Zeng, Dongzhi Ran, Hongbin Zhang, Zhigao Song, Ken H Song, Liangping Wu
Bariatric surgeries, including Roux-en-Y gastric bypass (RYGB) are currently the best treatment for obesity and obesity-related comorbidities, such as type 2 diabetes. However, the underlying mechanism of bariatric surgeries is not entirely understood. Further investigations are needed to improve the success rate and achieve sustained health benefits. Given that B cell dysregulation is a critical component of etiology in inflammatory diseases, whereas obesity and type 2 diabetes represent two major inflammatory disorders, we investigated the effect of RYGB on B cell inflammation...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27927966/tolerogenic-dendritic-cells-from-poorly-compensated-type-1-diabetes-patients-have-decreased-ability-to-induce-stable-antigen-specific-t-cell-hyporesponsiveness-and-generation-of-suppressive-regulatory-t-cells
#14
Klára Dáňová, Anna Grohová, Pavla Strnadová, David P Funda, Zdeněk Šumník, Jan Lebl, Ondřej Cinek, Štěpánka Průhová, Stanislava Koloušková, Barbora Obermannová, Lenka Petruželková, Anna Šedivá, Petra Fundová, Karsten Buschard, Radek Špíšek, Lenka Palová-Jelínková
Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing β cells leading to hyperglycemia that, in turn, specifically affects a patient's immune system. In this study, we prepared monocyte-derived tolDCs modulated by dexamethasone and vitamin D2 from 31 T1D patients with optimal glycemic control and 60 T1D patients with suboptimal glycemic control and assessed their tolerogenic properties in correlation with metabolic state of patients...
December 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27920091/interferon-gamma-limits-diabetogenic-cd8-t-cell-effector-responses-in-type-1-diabetes
#15
John P Driver, Jeremy J Racine, Cheng Ye, Deanna J Lamont, Brittney N Newby, Caroline G McPhee-Leeth, Harold D Chapman, Todd M Brusko, Yi-Guang Chen, Clayton E Mathews, David V Serreze
Type 1 diabetes development in the NOD mouse model is widely reported to be dependent on high-level production by autoreactive CD4(+) and CD8(+) T-cells of IFNγ, generally considered a pro-inflammatory cytokine. However, IFNγ can also participate in tolerance induction pathways, indicating it is not solely pro-inflammatory. This study addresses how IFNγ can suppress activation of diabetogenic CD8(+) T-cells. CD8(+) T-cells transgenically expressing the diabetogenic AI4 T-cell receptor (TCR) adoptively transferred disease to otherwise unmanipulated NOD...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27917204/modulation-of-immune-cells-and-th1-th2-cytokines-in-insulin-treated-type-2-diabetes-mellitus
#16
Magloire Pandoua Nekoua, Rufine Fachinan, Amidou K Atchamou, Odilon Nouatin, Daniel Amoussou-Guenou, Marcellin K Amoussou-Guenou, Kabirou Moutairou, Akadiri Yessoufou
BACKGROUND: The role of the immune system in insulin resistance associated with type 2 diabetes has been suggested. OBJECTIVES: We assessed the profile of Th1/Th2 cytokines along with the frequencies of immune cells in insulin-treated type 2 diabetic patients (T2DP). METHODS: 45 T2D patients and 43 age-matched healthy subjects were selected. Serum concentrations of T-helper type 1 (Th1) and Th2 cytokines and the frequencies of innate and adaptive immunity cells were assessed...
September 2016: African Health Sciences
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#17
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#18
Natalia Marek-Trzonkowska, Małgorzata Myśliwiec, Dorota Iwaszkiewicz-Grześ, Mateusz Gliwiński, Ilona Derkowska, Magdalena Żalińska, Maciej Zieliński, Marcelina Grabowska, Hanna Zielińska, Karolina Piekarska, Anna Jaźwińska-Curyłło, Radosław Owczuk, Agnieszka Szadkowska, Krystyna Wyka, Piotr Witkowski, Wojciech Młynarski, Przemysława Jarosz-Chobot, Artur Bossowski, Janusz Siebert, Piotr Trzonkowski
BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-) Tregs...
December 1, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27891128/immune-imbalances-in-non-alcoholic-fatty-liver-disease-from-general-biomarkers-and-neutrophils-to-interleukin-17-axis-activation-and-new-therapeutic-targets
#19
REVIEW
Feliciano Chanana Paquissi
Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27880731/smad4-in-t-cells-plays-a-protective-role-in-the-development-of-autoimmune-sj%C3%A3-gren-s-syndrome-in-the-nonobese-diabetic-mouse
#20
Donghee Kim, Jae Young Kim, Hee-Sook Jun
We investigated the role of Smad4, a signaling molecule of the TGF-beta pathway, in T cells on the pathology of Sjögren's syndrome (SS) in nonobese diabetic (NOD) mice, an animal model of SS. T cell-specific Smad4-deleted (Smad4fl/fl,CD4-Cre; Smad4 tKO) NOD mice had accelerated development of SS compared with wild-type (Smad4+/+,CD4-Cre; WT) NOD mice, including increased lymphocyte infiltration into exocrine glands, decreased tear and saliva production, and increased levels of autoantibodies at 12 weeks of age...
November 17, 2016: Oncotarget
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