PMID- 22596049 OWN - NLM STAT- MEDLINE DCOM- 20121105 LR - 20220317 IS - 1939-327X (Electronic) IS - 0012-1797 (Print) IS - 0012-1797 (Linking) VI - 61 IP - 9 DP - 2012 Sep TI - Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. PG - 2238-47 LID - 10.2337/db11-1274 [doi] AB - 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. FAU - Bertola, Adeline AU - Bertola A AD - Universite de Nice-Sophia Antipolis, Faculte de Medecine, Nice, France. FAU - Ciucci, Thomas AU - Ciucci T FAU - Rousseau, Deborah AU - Rousseau D FAU - Bourlier, Virginie AU - Bourlier V FAU - Duffaut, Carine AU - Duffaut C FAU - Bonnafous, Stephanie AU - Bonnafous S FAU - Blin-Wakkach, Claudine AU - Blin-Wakkach C FAU - Anty, Rodolphe AU - Anty R FAU - Iannelli, Antonio AU - Iannelli A FAU - Gugenheim, Jean AU - Gugenheim J FAU - Tran, Albert AU - Tran A FAU - Bouloumie, Anne AU - Bouloumie A FAU - Gual, Philippe AU - Gual P FAU - Wakkach, Abdelilah AU - Wakkach A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120517 PL - United States TA - Diabetes JT - Diabetes JID - 0372763 SB - IM MH - Adipose Tissue/*pathology/physiopathology MH - Adult MH - Animals MH - Cell Differentiation MH - Dendritic Cells/*physiology MH - Female MH - Humans MH - Insulin Resistance MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Middle Aged MH - Obesity/*pathology/physiopathology MH - Obesity, Morbid/pathology MH - T-Lymphocytes, Regulatory/physiology MH - Th17 Cells/physiology PMC - PMC3425417 EDAT- 2012/05/19 06:00 MHDA- 2012/11/06 06:00 PMCR- 2013/09/01 CRDT- 2012/05/19 06:00 PHST- 2012/05/19 06:00 [entrez] PHST- 2012/05/19 06:00 [pubmed] PHST- 2012/11/06 06:00 [medline] PHST- 2013/09/01 00:00 [pmc-release] AID - db11-1274 [pii] AID - 1274 [pii] AID - 10.2337/db11-1274 [doi] PST - ppublish SO - Diabetes. 2012 Sep;61(9):2238-47. doi: 10.2337/db11-1274. Epub 2012 May 17.