Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory <scp>T</scp> and <scp>T</scp>h17 cells

Moraes‐Vieira, Pedro M.; Larocca, Rafael A.; Bassi, Ênio José; Peron, Jean Pierre; Andrade-Oliveira, Vinícius; Wasinski, Frederick; Araújo, Ronaldo de Carvalho; Thornley, Thomas B.; Quintana, Francisco J.; Basso, Alexandre Salgado; Strom, Terry B.; Câmara, Niels Olsen Saraiva

doi:10.1002/eji.201343592

Cited by 89 publications

(69 citation statements)

References 57 publications

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“…In the absence of IL-6, TGF-β mediates the generation of immunosuppressive T reg cells [21,22] . The reciprocal balance between Foxp3+ T reg and Th17 cells is critical for immune homeostasis, and, if not properly regulated, Th17 cells can drive pathogenic inflammation [23] . High concentrations of IL-6 promote the differentiation of naive CD4+ T cells to form Th17 cells, and high concentrations of TGF-β promote the differentiation of naive CD4+ T cells to form Foxp3+ T reg cells through promoting expression of Foxp3 and suppressing expression of ROR-γt [12,24] .…”

Section: Discussionmentioning

confidence: 99%

Association of Pneumococcal Carriage and Expression of Foxp3+ Regulatory T Cells and Th17 Cells in the Adenoids of Children

Jiang

Zhang²,

Yang³

et al. 2015

Respiration

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tent with variations in levels of Foxp3 mRNA and retinoic acid receptor-related orphan receptor-γt mRNA in adenoidal mononuclear cells. Levels of IL-17A and IL-6 in adenoid tissue were higher in the pneumococcus-negative group, and the levels of TGF-β in adenoid tissue were lower in the pneumococcus-negative group compared to the pneumococcuspositive group. Pneumococcal carriage in children was closely associated with the expressions of Foxp3+ T reg and Th17 cells in the adenoid. Conclusion: Upregulation of Foxp3+ T reg cells might downregulate the production of Th17 cells in the adenoid, resulting in decreased scavenging of Streptococcus pneumoniae and chronic pneumococcal carriage.

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Section: Discussionmentioning

confidence: 99%

Association of Pneumococcal Carriage and Expression of Foxp3+ Regulatory T Cells and Th17 Cells in the Adenoids of Children

Jiang

Zhang²,

Yang³

et al. 2015

Respiration

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“…Mouse bone marrow cells were obtained as previously described (Moraes-Vieira et al ., 2013b). GM-CSF (R&D) at a concentration of 20 ng/mL was used for BMDC differentiation (Moraes-Vieira et al ., 2013b).…”

Section: Methodsmentioning

confidence: 99%

RBP4 Activates Antigen-Presenting Cells, Leading to Adipose Tissue Inflammation and Systemic Insulin Resistance

et al. 2014

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Insulin resistance is a major cause of diabetes and is highly associated with adipose tissue (AT) inflammation in obesity. RBP4, a retinol-transporter, is elevated in insulin resistance and contributes to increased diabetes risk. We aimed to determine the mechanisms for RBP4-induced insulin resistance. Here we show that RBP4 elevation causes AT inflammation by activating innate immunity which elicits an adaptive immune-response. RBP4-overexpressing mice (RBP4-Ox) are insulin-resistant and glucose-intolerant and have increased AT macrophage and CD4 T-cell infiltration. In RBP4-Ox, AT CD206+ macrophages express pro-inflammatory markers and activate CD4 T-cells while maintaining alternatively-activated macrophage markers. These effects result from direct activation of AT antigen-presenting cells (APCs) by RBP4 through a JNK-dependent pathway. Transfer of RBP4-activated APCs into normal mice is sufficient to induce AT inflammation, insulin resistance and glucose intolerance. Thus, RBP4 causes insulin resistance, at least partly, by activating AT APCs which induce CD4 T-cell Th1 polarization and AT inflammation.

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“…In addition to Treg-extrinsic mechanisms that impact obesity-associated IR, mouse studies identified peroxisome proliferator-activated receptor gamma as a Treg-intrinsic regulator that orchestrates Treg accumulation in visceral AT of lean animals [74]. Tregs are also regulated by leptin, a hormone increased in obesity and T2D that inhibits Treg proliferation [75, 76, 77], consistent with the demonstration that circulating human Treg frequency inversely correlates with leptin and body mass index (BMI) [17]. Cell-extrinsic regulation of Tregs is further mediated by IL-2 and IL-1β, which stimulate Tregs to differentiate into Th17-like cells [78].…”

Section: Lymphocytes As Sources Of Obesity/t2d–associated Inflammamentioning

confidence: 99%

Lymphocyte roles in metabolic dysfunction: of men and mice

Hogan

Nikolajczyk

2015

Trends in Endocrinology & Metabolism

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Type 2 diabetes (T2D) is a metabolic disease associated with obesity-related insulin resistance (IR) and chronic inflammation. Animal studies indicate IR can be caused and/or exacerbated by systemic/tissue-specific alterations in lymphocyte differentiation and function. Human studies also indicate obesity and/or inflammation promotes IR. Nevertheless, clinical trials with anti-inflammatory therapies have yielded modest impacts on established T2D. Unlike mouse models where obesity is predominantly associated with IR, 20–25% of obese people are metabolically healthy with high insulin sensitivity. The uncoupling of obesity from IR in humans but not in animal models advocates for a more comprehensive understanding of mediators/mechanisms in human obesity-promoted IR, and better integration of knowledge from human studies into animal experiments to efficiently pursue T2D prevention and treatment.

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Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells

Cited by 89 publications

References 57 publications

Association of Pneumococcal Carriage and Expression of Foxp3+ Regulatory T Cells and Th17 Cells in the Adenoids of Children

Association of Pneumococcal Carriage and Expression of Foxp3+ Regulatory T Cells and Th17 Cells in the Adenoids of Children

RBP4 Activates Antigen-Presenting Cells, Leading to Adipose Tissue Inflammation and Systemic Insulin Resistance

Lymphocyte roles in metabolic dysfunction: of men and mice

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