Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients

被引：295

作者：

Bertola, Adeline ^{[1
,2
]}

Ciucci, Thomas ^{[1
,3
]}

Rousseau, Deborah ^{[1
,2
]}

Bourlier, Virginie ^{[4
,5
]}

Duffaut, Carine ^{[4
,5
]}

Bonnafous, Stephanie ^{[1
,2
,6
]}

Blin-Wakkach, Claudine ^{[1
,3
]}

Anty, Rodolphe ^{[1
,2
,6
]}

Iannelli, Antonio ^{[1
,2
,6
]}

Gugenheim, Jean ^{[1
,2
,6
]}

Tran, Albert ^{[1
,2
,6
]}

Bouloumie, Anne ^{[4
,5
]}

Gual, Philippe ^{[1
,2
,6
]}

Wakkach, Abdelilah ^{[1
,3
]}

机构：

[1] Univ Nice Sophia Antipolis, Fac Med, Nice, France

[2] Fac Med Nice, INSERM, Equipe Complicat Hepat Obesite, U1065, F-06034 Nice, France

[3] Hop Archet, CNRS, LP2M, FRE3472, Nice, France

[4] Fac Med Toulouse, INSERM, Inst Malad Metab & Cardiovasc, U1048, F-31073 Toulouse, France

[5] Univ Paul Sabatier Toulouse III, Toulouse, France

[6] CHU Nice, Hop Archet, Dept Digestif, Nice, France

来源：

DIABETES | 2012年 / 61卷 / 09期

关键词：

REGULATORY T-CELLS; C-REACTIVE PROTEIN; METABOLIC SYNDROME; NONALCOHOLIC STEATOHEPATITIS; UNIQUE POPULATION; IMMUNE-RESPONSES; IN-VIVO; EXPRESSION; BLOOD; INFLAMMATION;

D O I：

10.2337/db11-1274

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 Ragl(-/-) 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. Diabetes 61:2238-2247,2012

引用

页码：2238 / 2247

页数：10

共 40 条

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