Obesity predisposes to Th17 bias

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 ex...

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Bibliographic Details
Published in:European journal of immunology 2009-09, Vol.39 (9), p.2629-2635
Main Authors: Winer, Shawn, Paltser, Geoff, Chan, Yin, Tsui, Hubert, Engleman, Edgar, Winer, Daniel, Dosch, H.-Michael
Format: Article
Language:English
Subjects:
Animals
Autoimmunity
Colitis - etiology
Colitis - immunology
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental - etiology
Encephalomyelitis, Autoimmune, Experimental - immunology
Glycoproteins - pharmacology
IL‐17
Interleukin-17 - immunology
Interleukin-6 - immunology
Interleukin-6 - metabolism
Male
Mice
Mice, Inbred C57BL
Myelin-Oligodendrocyte Glycoprotein
Obesity
Obesity - complications
Obesity - immunology
Peptide Fragments - pharmacology
T-Lymphocytes, Helper-Inducer - drug effects
T-Lymphocytes, Helper-Inducer - immunology
Trinitrobenzenesulfonic Acid - pharmacology
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Summary: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.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200838893