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-alpha, IL-6 and TGF-beta 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.
Winer
Shawn
S
Neuroscience and Mental Health program, Research Institute, The Hospital for Sick Children, University of Toronto Departments of Pediatrics & Immunology, Toronto, Ontario Canada.
Paltser
Geoff
G
Chan
Yin
Y
Tsui
Hubert
H
Engleman
Edgar
E
Winer
Daniel
D
Dosch
H-Michael
HM
D000818:Animals; D003092:Colitis / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology*; D006023:Glycoproteins / Q000494:pharmacology; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D009765:Obesity / Q000150:complications* / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D006023:Glycoproteins; D020381:Interleukin-17; D015850:Interleukin-6; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D014302:Trinitrobenzenesulfonic Acid