Obesity predisposes to Th17 bias

Authors

  • Shawn Winer,

    1. Neuroscience and Mental Health program, Research Institute, The Hospital for Sick Children, University of Toronto Departments of Pediatrics & Immunology, Toronto, Ontario Canada
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    • These authors contributed equally to this work.

  • Geoff Paltser,

    1. Neuroscience and Mental Health program, Research Institute, The Hospital for Sick Children, University of Toronto Departments of Pediatrics & Immunology, Toronto, Ontario Canada
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    • These authors contributed equally to this work.

  • Yin Chan,

    1. Neuroscience and Mental Health program, Research Institute, The Hospital for Sick Children, University of Toronto Departments of Pediatrics & Immunology, Toronto, Ontario Canada
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  • Hubert Tsui,

    1. Neuroscience and Mental Health program, Research Institute, The Hospital for Sick Children, University of Toronto Departments of Pediatrics & Immunology, Toronto, Ontario Canada
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  • Edgar Engleman,

    1. Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA
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  • Daniel Winer,

    1. Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA
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  • H.-Michael Dosch

    Corresponding author
    1. Neuroscience and Mental Health program, Research Institute, The Hospital for Sick Children, University of Toronto Departments of Pediatrics & Immunology, Toronto, Ontario Canada
    • The Hospital For Sick Children NMH Program, 555 University Ave, Toronto, ON, Canada M5G 1X8 Fax: +1-416-813-6255
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Abstract

Obesity is associated with numerous inflammatory conditions including atherosclerosis, autoimmune disease and cancer. Although the precise mechanisms are unknown, obesity-associated rises in TNF-α, IL-6 and TGF-β are believed to contribute. Here we demonstrate that obesity selectively promotes an expansion of the Th17 T-cell sublineage, a subset with prominent pro-inflammatory roles. T-cells from diet-induced obese mice expand Th17 cell pools and produce progressively more IL-17 than lean littermates in an IL-6-dependent process. The increased Th17 bias was associated with more pronounced autoimmune disease as confirmed in two disease models, EAE and trinitrobenzene sulfonic acid colitis. In both, diet-induced obese mice developed more severe early disease and histopathology with increased IL-17+ T-cell pools in target tissues. The well-described association of obesity with inflammatory and autoimmune disease is mechanistically linked to a Th17 bias.

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