title: Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients.
abstract: T-cell regulation in adipose tissue provides a link between inflammation and insulin resistance. Because of alterations in adipose tissue T-cell composition in obesity, we aimed to identify the antigen-presenting cells in adipose tissue of obese mice and patients with insulin resistance. Dendritic cells (DCs) and T cells were studied in mice and in two cohorts of obese patients. In lean mice, only CD11c(+) DCs were detected in adipose tissue. Adoptive transfer of naive CD4(+) T cells in Rag1(-/-) mice led to a predominant Th1 response in adipose tissue. In contrast, during obesity DCs (human CD11c(+)CD1c(+) and mouse CD11c(high)F4/80(low)) accumulated in adipose tissue. CD11c(high)F4/80(low) DCs from obese mice induced Th17 differentiation. In patients, the presence of CD11c(+)CD1c(+) DCs correlated with the BMI and with an elevation in Th17 cells. In addition, these DCs led to ex vivo Th17 differentiation. CD1c gene expression further correlated with homeostatic model assessment-insulin resistance in the subcutaneous adipose tissue of obese patients. We show for the first time the presence and accumulation of specific DCs in adipose tissue in mouse and human obesity. These DCs were functional and could be important regulators of adipose tissue inflammation by regulating the switch toward Th17 cell responses in obesity-associated insulin resistance.
authors.affiliation: Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Bertola
authors.forename: Thomas
authors.initials: T
authors.lastname: Ciucci
authors.forename: Déborah
authors.initials: D
authors.lastname: Rousseau
authors.forename: Virginie
authors.initials: V
authors.lastname: Bourlier
authors.forename: Carine
authors.initials: C
authors.lastname: Duffaut
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bonnafous
authors.forename: Claudine
authors.initials: C
authors.lastname: Blin-Wakkach
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Anty
authors.forename: Antonio
authors.initials: A
authors.lastname: Iannelli
authors.forename: Jean
authors.initials: J
authors.lastname: Gugenheim
authors.forename: Albert
authors.initials: A
authors.lastname: Tran
authors.forename: Anne
authors.initials: A
authors.lastname: Bouloumié
authors.forename: Philippe
authors.initials: P
authors.lastname: Gual
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Wakkach
mesh_terms: D000273:Adipose Tissue / Q000473:pathology* / Q000503:physiopathology; D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000473:pathology* / Q000503:physiopathology; D009767:Obesity, Morbid / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D058504:Th17 Cells / Q000502:physiology