Identification of Adipose Tissue Dendritic Cells Correlated With Obesity-Associated Insulin-Resistance and Inducing Th17 Responses in Mice and Patients
- Adeline Bertola1,2,
- Thomas Ciucci1,3,
- Déborah Rousseau1,2,
- Virginie Bourlier4,5,
- Carine Duffaut4,5,
- Stéphanie Bonnafous1,2,6,
- Claudine Blin-Wakkach1,3,
- Rodolphe Anty1,2,6,
- Antonio Iannelli1,2,6,
- Jean Gugenheim1,2,6,
- Albert Tran1,2,6,
- Anne Bouloumié4,5,
- Philippe Gual1,2,6 and
- Abdelilah Wakkach1,3⇓
- 1Université de Nice-Sophia Antipolis, Faculté de Médecine, Nice, France
- 2INSERM, U1065, Equipe Complications hépatiques de l’obésité, Nice, France
- 3LP2M-CNRS-FRE3472, Hôpital de l'Archet, Nice, France
- 4INSERM, U1048, Institut des maladies métaboliques et cardiovasculaires, Toulouse, France
- 5Université Paul Sabatier Toulouse-III, Toulouse, France
- 6Centre Hospitalier Universitaire de Nice, Hôpital de l’Archet, Département Digestif, Nice, France
- Corresponding author: Abdelilah Wakkach, , or Philippe Gual, .
A.B. and T.C. contributed equally to this study.
P.G. and A.W. contributed equally to this study.
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 CD11chighF4/80low) accumulated in adipose tissue. CD11chighF4/80low 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.
- Received September 13, 2011.
- Accepted March 14, 2012.
- © 2012 by the American Diabetes Association.
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