Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice

Sun, Yuchun; Tian, Tian; Gao, Juan; Liu, Xiaoqian; Hou, Huilian; Cao, Runjing; Li, Bin; Quan, Moyuan; Guo, Li

doi:10.1016/j.jneuroim.2016.01.014

Cited by 109 publications

(69 citation statements)

References 37 publications

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“…In HaCaT cells, metformin inhibits mTORC1 activity and the expression of IL‐6 and tumour necrosis factor (TNF)‐α . Metformin attenuates inflammation in murine autoimmune arthritis, graft‐versus‐host disease, IBD and autoimmune encephalomyelitis . In these models, metformin decreased Th17 cells and increased Treg cell differentiation …”

Section: Therapeutic Agents Affect the T Helper 17 Cell/regulatory T‐mentioning

confidence: 99%

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

et al. 2018

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Section: Therapeutic Agents Affect the T Helper 17 Cell/regulatory T‐mentioning

confidence: 99%

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

et al. 2018

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“…Treating underlying metabolic syndrome with classic anti-diabetic drugs such as metformin and pioglitazone ameliorates metabolic disturbances, reduces MRI-evident lesion frequency and dampens T-cell pro-inflammatory response in MS patients (Negrotto et al, 2016). Metformin also reduces disease severity and pro-inflammatory response in an experimental model of MS (Nath et al, 2009; Sun et al, 2016). Recently, obese MS patients have been shown to have a less pronounced response to interferon treatment (Kvistad et al, 2015) underlining the need for further investigation of metabolic disturbances and pharmacological targets for treating MS through improved metabolic control.…”

Section: Introductionmentioning

confidence: 99%

Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats

et al. 2016

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Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE).Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11) or if exceeding humane endpoint (clinical score ≥4). Protein levels of manganese superoxide dismutase (MnSOD), amyloid precursor protein (APP), and glial fibrillary acidic protein (GFAP) were determined.Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0) by 2 days and markedly reduced disease severity (median clinical score 2 vs. 5; p = 0.0003). Fourteen of 15 (93%) of vehicle-treated rats reached the humane endpoint (clinical score ≥4) by day 11 compared to 5 of 15 (33%) of liraglutide-treated rats (p = 0.0004). Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p < 0.01) and reduced the neurodegenerative marker APP (p = 0.036) in the brain. GFAP levels were not significantly changed with drug treatment (p = 0.09).Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor agonists should be investigated further as a potential therapy for MS.

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“…Further, memory CD8+ T-cell development is also supported by activating the energy sensor AMPK pathway (71, 72). FAO has clinical implications for memory CD8+ T as well as for T reg cells (73). In fact, administration of metformin or the mTOR inhibitor rapamycin, reduce mTOR activity and induce AMPK phophorylation that in turn perform lipid oxidation and enhance the formation of T m cells after infection and increase T reg responses in asthma model (74, 75).…”

Section: Distinct Metabolic Programs For T Cells Differentiation and mentioning

confidence: 99%

Impact of Metabolism in on T-Cell Differentiation and Function and Cross Talk with Tumor Microenvironment

2017

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The immune system and metabolism are highly integrated and multilevel interactions between metabolic system and T lymphocyte signaling and fate exist. Accumulating evidence indicates that the regulation of nutrient uptake and utilization in T cells is critically important for the control of their differentiation and manipulating metabolic pathways in these cells can shape their function and survival. This review will discuss some potential cell metabolism pathways involved in shaping T lymphocyte function and differentiation. It will also describe show subsets of T cells have specific metabolic requirements and signaling pathways that contribute to their respective function. Examples showing the apparent similarity between cancer cell metabolism and T cells during activation are illustrated and finally some mechanisms being used by tumor microenvironment to orchestrate T-cell metabolic dysregulation and the subsequent emergence of immune suppression are discussed. We believe that targeting T-cell metabolism may provide an additional opportunity to manipulate T-cell function in the development of novel therapeutics.

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Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice

Cited by 109 publications

References 37 publications

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats

Impact of Metabolism in on T-Cell Differentiation and Function and Cross Talk with Tumor Microenvironment

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