Dynamic changes of the Th17/Tc17 and regulatory T cell populations interfere in the experimental autoimmune diabetes pathogenesis

Yaochite, Juliana Navarro Ueda; Caliári-Oliveira, Carolina; Davanso, Mariana Rodrigues; Carlos, Daniela; Malmegrim, Kelen Cristina Ribeiro; Cardoso, Cristina Ribeiro de Barros; Ramalho, Leandra Náira Zambelli; Palma, Patrícia Vianna Bonini; Silva, João; Cunha, Fernando; Covas, Dimas Tadeu; Voltarelli, Júlio César

doi:10.1016/j.imbio.2012.05.010

Cited by 51 publications

(48 citation statements)

References 67 publications

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“…Immune responses play an important role in MLD-STZ-induced diabetes (Gao et al, 2013; Barbu-Tudoran et al, 2013; Yaochite et al, 2013), and in TCDD-mediated toxicity (Mandal, 2005; Shan et al, 2014). Thus, flow cytometric analysis of splenocyte differentials was undertaken.…”

Section: Resultsmentioning

confidence: 99%

TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

Lefever

Chen

et al. 2016

Toxicology and Applied Pharmacology

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An increasing body of evidence has shown the important role of the gut microbiome in mediating toxicity following environmental contaminant exposure. The goal of this study was to determine if the adverse metabolic effects of chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure would be sufficient to exacerbate hyperglycemia, and to further determine if these outcomes were attributable to the gut microbiota alteration. Adult male CD-1 mice were exposed to TCDD (6 μg/kg body weight biweekly) by gavage and injected (i.p.) with STZ (4 × 50 mg/kg body weight) to induced hyperglycemia. 16S rRNA sequencing was used to characterize the changes in the microbiome community composition. Glucose monitoring, flow cytometry, histopathology, and organ characterization were performed to determine the deleterious phenotypic changes of TCDD exposure. Chronic TCDD treatment did not appear to exacerbate STZ-induced hyperglycemia as blood glucose levels were slightly reduced in the TCDD treated mice; however, polydipsia and polyphagia were observed. Importantly, TCDD exposure caused a dramatic change in microbiota structure, as characterized at the phylum level by increasing Firmicutes and decreasing Bacteroidetes while at the family level most notably by increasing Lactobacillaceae and Desulfovibrionaceae, and decreasing Prevotellaceae and ACK M1. The changes in microbiota were further found to be broadly associated with phenotypic changes seen from chronic TCDD treatment. In particular, the phylum level Bacteroidetes to Firmicutes ratio negatively correlated with both liver weight and liver pathology, and positively associated with %CD3+NK+ T cells, a key mediator of host-microbial interactions. Collectively, these findings suggest that the dysregulated gut microbiome may contribute to the deleterious effects (e.g., liver toxicity) seen with TCDD exposure.

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Section: Resultsmentioning

confidence: 99%

TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

Lefever

Chen

et al. 2016

Toxicology and Applied Pharmacology

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“…Immune responses play an important role in MLD-STZ-induced diabetes (Thomas-Vaslin et al, 1997; Ablamunits et al, 1999; Gao et al, 2013; Barbu-Tudoran et al, 2013; Yaochite et al, 2013). Thus, flow cytometric analysis of splenocyte differentials was undertaken.…”

Section: Resultsmentioning

confidence: 99%

“…Depending on dose and other factors (e.g., diet), streptozotocin (STZ)-induced diabetes can be considered either T1D or T2D (Reed et al, 2000; Zhang et al, 2008; Gao et al, 2011; Muller et al , 2011; Shpilberg et al, 2012; Ramos-Rodriguez et al, 2013). The multiple low dose (MLD)-STZ-induced diabetes in mice that do not develop diabetes spontaneously is also a disease of immune origin since it is associated with a secondary autoimmune insulitis following apoptotic injury of the pancreatic β-cells (Thomas-Vaslin et al, 1997; Ablamunits et al, 1999; Gao et al, 2013; Barbu-Tudoran et al, 2013; Yaochite et al, 2013), which confers this model the ability to detect nutrient or toxicant modulation of diabetes.…”

Section: Introductionmentioning

confidence: 99%

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

Guo

Wang

Xiong

et al. 2014

Toxicology and Applied Pharmacology

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Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes.

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“…In accordance with this, our research group reported recently the important role of Th17 cells during the early stages of diabetes development in STZ model using mice lacking the expression of IL-17 receptor. Six days after diabetes induction, IL-17 receptor deficient mice showed impairment in STZ-induced diabetes progression, reduced peri-insulitis and beta cells preservation when compared with wild-type mice, suggesting that IL-17 signaling contributes to initiation of diabetes development [51]. Collectively, these reports indicate that Th17 cells may be directly involved in inflammatory response against pancreatic islets and the suppression of Th17 cells may represent a possible target for the prevention or reversal of T1D.…”

Section: Van Et Al [71]mentioning

confidence: 81%

Th17 cell-Mediated Responses in Type 1 Diabetes Pathogenesis

J.N.U¹

2013

J Clin Cell Immunol

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Type 1 diabetes (T1D) is an autoimmune disease characterized by a selective destruction of insulin-producing pancreatic beta cells. In general, Th1 cytokines are involved in the development of autoimmune diseases, whereas Th2 and regulatory cytokines result in disease prevention. More recently, a new population of IL-17-producing CD4+ T cells has been proposed to represent a distinct T helper cell lineage, named Th17 cells. Th17 cells are critically involved in the development of many autoimmune diseases; however, the exact role of this T cell subset in T1D pathogenesis remains controversial. Here, we review the conflicting evidences about a possible participation of Th17 cells in T1D development and progression, both in diabetic patients and experimental diabetes models.

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Dynamic changes of the Th17/Tc17 and regulatory T cell populations interfere in the experimental autoimmune diabetes pathogenesis

Cited by 51 publications

References 67 publications

TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

Th17 cell-Mediated Responses in Type 1 Diabetes Pathogenesis

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