☆ 4.6 Review

Multifaceted roles of T cells in obesity and obesity-related complications: A narrative review

OBESITY REVIEWS (2023)

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Summary: IL-23R(+) gamma delta T cells predominantly found in the aortic root promote early atherosclerotic lesion formation, plaque necrosis, and inflammation at this site. Targeting IL-23R may be explored as a therapeutic approach to mitigate atherosclerotic lesion development.

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Summary: The rapid growth of obesity worldwide has had a significant impact on the prevalence of chronic kidney disease, particularly in developing countries. Obesity has been strongly associated with chronic kidney disease and is an independent risk factor for kidney disease. Histological changes in obesity-induced renal injury include glomerular or tubular hypertrophy, focal segmental glomerulosclerosis or bulbous sclerosis. Inflammation, renal hemodynamic changes, insulin resistance, and lipid metabolism disorders are all involved in the development and progression of obesity-induced nephropathy. However, there is currently no targeted treatment for obesity-related kidney disease. This review presents the use of RAS inhibitors, SGLT2 inhibitors, and melatonin to treat obesity-induced kidney injury. Melatonin, in particular, has shown potential in protecting against kidney damage caused by obesity through inhibiting inflammation and oxidative stress.

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An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism

Zengdi Zhang et al.

Summary: This article investigates the role of the O-GlcNAc transferase (OGT)-STAT5 axis in regulating the immunomodulatory function and metabolic homeostasis of Treg cells. The results show that OGT deficiency in Treg cells makes mice more susceptible to high-fat diet-induced obesity and insulin resistance, while constitutive STAT5 activation in Treg cells protects against adipose tissue expansion and impaired glucose and insulin metabolism. Targeting the OGT-STAT5 axis can enhance Treg cell function to combat obesity and related metabolic disorders.

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Leptin favors Th17/Treg cell subsets imbalance associated with allergic asthma severity

Carolina M. Vollmer et al.

Summary: The severity of AA in obese patients is associated with the expansion of Th17-like and Th2/Th17 cells, and a decrease in regulatory CD4(+)T cell subsets, likely mediated by overproduction of leptin.

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Elizabeth Greene et al.

Summary: Disorders of systemic metabolism, such as obesity, can disrupt immune function and increase the risk and severity of viral infections. Specifically, individuals with obesity, particularly severe obesity, have a higher risk of poor outcomes from influenza and SARS-CoV-2 infections. T cells play a critical role in obesity-associated immune dysfunction, and altered T cell metabolism may contribute to this. Treatment with the metabolic drug metformin has shown promise in reversing abnormal T cell metabolism and improving outcomes to viral infection.

FRONTIERS IN IMMUNOLOGY (2022)

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The Role of T Cells in Obesity-Associated Inflammation and Metabolic Disease

Chan-Su Park et al.

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Increasing Imbalance of Treg/Th17 Indicates More Severe Glucose Metabolism Dysfunction in Overweight/obese Patients

Jie Wen et al.

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Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma

Yimin Guo et al.

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Tregs facilitate obesity and insulin resistance via a Blimp-1/IL-10 axis

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Summary: IL-10, produced by CD4(+)Foxp3(+) regulatory T cells, can suppress adipocyte beiging, leading to reduced insulin resistance and obesity. Loss of IL-10 in Tregs, through the transcription factor Blimp-1, resulted in improved metabolic outcomes in high-fat diet-fed mice. This highlights the important role of Treg-derived IL-10 in regulating adipose tissue homeostasis.

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P300/CBP Associated Factor (PCAF) Deficiency Enhances Diet-Induced Atherosclerosis in ApoE3*Leiden Mice via Systemic Inhibition of Regulatory T Cells

Alwin de Jong et al.

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PKM2-dependent metabolic skewing of hepatic Th17 cells regulates pathogenesis of non-alcoholic fatty liver disease

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Associations of TNFA, IL17A, and RORC mRNA expression levels in peripheral blood leukocytes with obesity-related asthma in adolescents

Jose J. Leija-Martinez et al.

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Dexamethasone-Induced FKBP51 Expression in CD4+ T-Lymphocytes Is Uniquely Associated With Worse Asthma Control in Obese Children With Asthma

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A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function

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CELL METABOLISM (2017)

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Article Immunology

Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice

F. M. C. Silva et al.

CLINICAL AND EXPERIMENTAL IMMUNOLOGY (2017)

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Review Immunology

IL-17+ γδ T cells as kick-starters of inflammation

Pedro H. Papotto et al.

NATURE IMMUNOLOGY (2017)

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Article Cell Biology

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals

Claudio Mauro et al.

CELL METABOLISM (2017)

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Article Gastroenterology & Hepatology

Elevated IL-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous IL-33 promotes eosinophilic esophagitis development in mice

L. M. Judd et al.

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2016)

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Article Allergy

Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production

Monika Majewska-Szczepanik et al.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2016)

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Review Immunology

Metabolic pathways in T cell activation and lineage differentiation

Luis Almeida et al.

SEMINARS IN IMMUNOLOGY (2016)

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Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression

Chih-Hao Chang et al.

CELL (2015)

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Article Cell Biology

The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease

Lucile Garidou et al.

CELL METABOLISM (2015)

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Article Medicine, Research & Experimental

Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients

Isabelle Magalhaes et al.

JOURNAL OF CLINICAL INVESTIGATION (2015)

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Review Immunology

Fatty acid metabolism in the regulation of T cell function

Matthias Lochner et al.

TRENDS IN IMMUNOLOGY (2015)

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Article Immunology

Type 2 inflammation in asthma - present in most, absent in many

John V. Fahy

NATURE REVIEWS IMMUNOLOGY (2015)

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Article Physiology

Differential coupling of KLF10 to Sin3-HDAC and PCAF regulates the inducibility of the FOXP3 gene

Yuning Xiong et al.

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY (2014)

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Article Immunology

Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin

Jan Mauer et al.

NATURE IMMUNOLOGY (2014)

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Review Immunology

Human memory T cells: generation, compartmentalization and homeostasis

Donna L. Farber et al.

NATURE REVIEWS IMMUNOLOGY (2014)

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Article Biochemistry & Molecular Biology

Diet-Induced Obesity Alters Immune Cell Infiltration and Expression of Inflammatory Cytokine Genes in Mouse Ovarian and Peri-Ovarian Adipose Depot Tissues

J. Nteeba et al.

MOLECULAR REPRODUCTION AND DEVELOPMENT (2013)

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Review Immunology

Macrophages in atherosclerosis: a dynamic balance

Kathryn J. Moore et al.

NATURE REVIEWS IMMUNOLOGY (2013)

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Article Biochemistry & Molecular Biology

IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction

Makoto Kudo et al.

NATURE MEDICINE (2012)

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Review Biochemistry & Molecular Biology

Asthma phenotypes: the evolution from clinical to molecular approaches

Sally E. Wenzel

NATURE MEDICINE (2012)

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Article Oncology

Reduced Paneth cell antimicrobial protein levels correlate with activation of the unfolded protein response in the gut of obese individuals

Caroline M. Hodin et al.

JOURNAL OF PATHOLOGY (2011)

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Article Multidisciplinary Sciences

Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis

Khoa D. Nguyen et al.

NATURE (2011)

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Review Immunology

T cell exhaustion

E. John Wherry

NATURE IMMUNOLOGY (2011)

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Review Immunology

Regulatory T cells in many flavors control asthma

A. Ray et al.

MUCOSAL IMMUNOLOGY (2010)

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Article Cardiac & Cardiovascular Systems

T Cell-Mediated Inflammation in Adipose Tissue Does Not Cause Insulin Resistance in Hyperlipidemic Mice

Ariane Sultan et al.

CIRCULATION RESEARCH (2009)

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Review Medicine, Research & Experimental

Role of β7 Integrins in Intestinal Lymphocyte Homing and Retention

G. Gorfu et al.

CURRENT MOLECULAR MEDICINE (2009)

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Article Immunology

Differential Roles of Interleukin-17A and-17F in Host Defense against Mucoepithelial Bacterial Infection and Allergic Responses

Harumichi Ishigame et al.

IMMUNITY (2009)

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Article Biochemistry & Molecular Biology

Kruppel-like Factor KLF10 Targets Transforming Growth Factor-β1 to Regulate CD4+CD25- T Cells and T Regulatory Cells

Zhuoxiao Cao et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

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CCR1 and CCR5 promote hepatic fibrosis in mice

Ekihiro Seki et al.

JOURNAL OF CLINICAL INVESTIGATION (2009)

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Article Biochemistry & Molecular Biology

Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters

Markus Feuerer et al.

NATURE MEDICINE (2009)

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Normalization of obesity-associated insulin resistance through immunotherapy

Shawn Winer et al.

NATURE MEDICINE (2009)

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Article Gastroenterology & Hepatology

Exacerbating role of γδ T cells in chronic colitis of T-cell receptor a mutant mice

Masanobu Nanno et al.

GASTROENTEROLOGY (2008)

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Review Immunology

CCR7 and its ligands:: balancing immunity and tolerance

Reinhold Foerster et al.

NATURE REVIEWS IMMUNOLOGY (2008)

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Article Multidisciplinary Sciences

CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages

Machteld M. Tiemessen et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2007)

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Crystal structure of the IL-15-IL-15Rα complex, a cytokine-receptor unit presented in trans

Mami Chirifu et al.

NATURE IMMUNOLOGY (2007)

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Review Oncology

Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms

EE Calle et al.

NATURE REVIEWS CANCER (2004)

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Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001

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JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2003)

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