Adipocyte‐derived lipids modulate CD4⁺ T‐cell function

Abstract

Adipose tissue contains several immune cells whose number and phenotype vary depending on the adiposity. In the present study, we show that IFN-γ + CD4 + T cells are enriched in human adipose tissue compared with in blood. To gain insight into the underlying mechanisms, we investigated the possibility that human adipocytes modulate CD4 + T-cell cytokine production and proliferation and show that CD4 + T cells produced increased levels of IFN-γ when activated in the presence of adipocytes. This effect was mediated by soluble mediators, as shown in transwell and adipocyte-conditioned medium (ACM) transfer experiments. Additionally, ACM induced increased proliferation of CD4 + T cells upon activation. Intriguingly, the proliferation-enhancing effect resided mainly in the lipid fraction of ACM, as shown upon separation of the protein and lipid fraction. Further separation of these lipids based on polarity revealed that the modulatory effect is confined to fractions containing free fatty acids. All identified fatty acids were able to individually enhance T-cell proliferation. These data indicate that adipocytes can modulate CD4 + T-cell function through the release of lipids. Remarkably, free fatty acids were the most prominent modulators of T-cell proliferation, possibly leading to an accumulation of these cells in adipose tissue. Keywords: Adipocytes r CD4 + T cells r Lipids r ObesityAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAdipose tissue is composed of adipocytes, which are primarily involved in lipid storage and release, and the stromal vascular fraction (SVF). The composition of the SVF varies, depending on the localization of the adipose tissue and the degree of adiposity of the individual, but it typically contains a large variety Correspondence: Dr. Andreea Ioan-Facsinay e-mail: A.Ioan@lumc.nl of cells, including progenitor cells, fibroblasts, endothelial cells, nerve cells, and immune 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. However, adipocytes can release a large number of soluble mediators with different biologica...

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