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Cell Biology/Signaling |
From the Institut National de la Santé et de la Recherche Médicale (INSERM), U858, Toulouse, France, Université Toulouse III Paul Sabatier, Institut de Médecine Moléculaire de Rangueil, Equipe n°1 AVENIR (C.D., A.Z.-G., V.B., P.D., M.M., C.S., M.L., J.G., A.B.), Chirurgie générale et digestive (P.C.), CHU Purpan, Toulouse, France.
Correspondence to Anne Bouloumié, Equipe 1 AVENIR/INSERM U858, Hôpital Rangueil Bat L4, BP 84225, 31432 Toulouse Cedex 04, France. E-mail anne.bouloumie{at}inserm.fr
Objective— Adipose tissue (AT) plays a major role in the low-grade inflammatory state associated with obesity. The aim of the present study was to characterize the human AT lymphocytes (ATLs) and to analyze their interactions with adipocytes.
Methods and Results— Human ATL subsets were characterized by flow cytometry in subcutaneous ATs from 92 individuals with body mass index (BMI) ranging from 19 to 43 kg/m2 and in paired biopsies of subcutaneous and visceral AT from 45 class II/III obese patients. CD3+ ATLs were composed of effector and memory CD4+ helper and CD8+ cytotoxic T cells. The number of ATLs correlated positively with BMI and was higher in visceral than subcutaneous AT. Mature adipocytes stimulated the migration of ATLs and released the chemokine CCL20, the receptor of which (CCR6) was expressed in ATLs. The expression of adipocyte CCL20 was positively correlated with BMI and increased in visceral compared to subcutaneous adipocytes. ATLs expressed inflammatory markers and released interferon gamma (IFN
). Progenitor and adipocyte treatment with ATL-conditioned media reduced the insulin-mediated upregulation of lipogenic enzymes, an effect involving IFN
.
Conclusions— Therefore, crosstalk occurs between adipocytes and lymphocytes within human AT involving T cell chemoattraction by adipocytes and modulation of lipogenesis by ATLs.
Obesity in humans is associated with an accumulation of helper and cytotoxic T lymphocytes in adipose tissue. Crosstalk occurs between human mature adipocytes and lymphocytes within human AT involving T cell chemoattraction by adipocytes via the couple CCL20/CCR6 and modulation of the insulin-stimulated lipogenesis by ATLs through interferon gamma.
Key Words: inflammation visceral fat macrophages T lymphocyte subsets CCR6
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