Interplay Between Human Adipocytes and T Lymphocytes in Obesity

Abstract

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/m 2 and in paired biopsies of subcutaneous and visceral AT from 45 class II/III obese patients. CD3ϩ ATLs were composed of effector and memory CD4 ϩ helper and CD8 ϩ 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 insulinmediated 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.

Adipocyte‐derived lipids modulate CD4+ T‐cell function

“…We and others have previously shown that a significant percentage of CD4 + T cells in adipose tissue have a memory Th1 phenotype [3,8]. In this study, we further investigate this T-cell population and show that there is an enrichment of IFN-γ-secreting cells in adipose tissue compared with peripheral blood from the same individuals.…”

“…Moreover, some adipocytederived soluble mediators, such as leptin [10, have been shown to modulate differentiation or cytokine production by CD4 + T cells. However, adipocytes can release a large number of soluble mediators with different biological functions and their global effect on T cells is unknown.We and others have previously shown that a significant percentage of CD4 + T cells in adipose tissue have a memory Th1 phenotype [3,8]. In this study, we further investigate this T-cell population and show that there is an enrichment of IFN-γ-secreting cells in adipose tissue compared with peripheral blood from the same individuals.…”

“…Adipose tissue T cells have been previously shown to be present in the vicinity of adipocytes [3]. Moreover, some adipocytederived soluble mediators, such as leptin [10, have been shown to modulate differentiation or cytokine production by CD4 + T cells.…”

“…Among the immune cells described in adipose tissue, macrophages and T cells are the most abundant, but other cells, like NK cells, mast cells, and B cells have also been described (reviewed in [1]). While the precise role of these cells in the adipose tissue is largely unknown, there is increasing evidence that cross-talk between immune cells and adipocytes exists and that the immune cells can influence the metabolic functions of the resident adipocytes (reviewed in [1] [2,3], or local differentiation/proliferation of resident T cells [5] under the influence of the adipose tissue environment could constitute underlying mechanisms for changes in the adipose tissue CD4 + T-cell population in obesity.Adipose tissue T cells have been previously shown to be present in the vicinity of adipocytes [3]. Moreover, some adipocytederived soluble mediators, such as leptin [10, have been shown to modulate differentiation or cytokine production by CD4 + T cells.…”

Le tissu adipeux

“…L'importance physiopathologique de ces changements est illustrée par le fait que l'inactivation des T CD8 + [13] ou l'induction des lymphocytes Th2 ou des Treg [14,15] diminue l'inflammation dans le tissu adipeux des souris DIO. Chez l'homme, une étude montre l'augmentation des lymphocytes T CD8 + et lymphocytes CD4 + avec le degré d'adiposité dans le tissu adipeux [16]. L'ensemble de ces observations suggèrent l'existence d'un jeu complexe d'influence entre les différents acteurs cellulaires de l'immunité innée (neutrophiles, mastocytes), adaptative (lymphocytes) ou à l'interface des deux systèmes (NKT).…”