Adipose Tissue Macrophages Function As Antigen-Presenting Cells and Regulate Adipose Tissue CD4+ T Cells in Mice

Abstract

The proinflammatory activation of leukocytes in adipose tissue contributes to metabolic disease. How crosstalk between immune cells initiates and sustains adipose tissue inflammation remains an unresolved question. We have examined the hypothesis that adipose tissue macrophages (ATMs) interact with and regulate the function of T cells. Dietary obesity was shown to activate the proliferation of effector memory CD4+ T cells in adipose tissue. Our studies further demonstrate that ATMs are functional antigen-presenting cells that promote the proliferation of interferon-γ–producing CD4+ T cells in adipose tissue. ATMs from lean and obese visceral fat process and present major histocompatibility complex (MHC) class II–restricted antigens. ATMs were sufficient to promote proliferation and interferon-γ production from antigen-specific CD4+ T cells in vitro and in vivo. Diet-induced obesity increased the expression of MHC II and T-cell costimulatory molecules on ATMs in visceral fat, which correlated with an induction of T-cell proliferation in that depot. Collectively, these data indicate that ATMs provide a functional link between the innate and adaptive immune systems within visceral fat in mice.

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

“…AT macrophages also process and present antigen on MHCII molecules and express costimulatory molecules (34,35). Macrophage-T-cell interactions result in the polarization of naïve T cells toward IFN-g-producing Th1 cells (34,35). Furthermore, AT B cells may act as APCs that induce MHCII-dependent T-cell activation as well as T-celldependent antigen production, which is further promoted by the expression of multiple costimulatory molecules on B cells (36).…”

“…Although AT DCs induce Th17 differentiation of naïve T cells, detailed knowledge of the underlying mechanisms is lacking. AT macrophages also process and present antigen on MHCII molecules and express costimulatory molecules (34,35). Macrophage-T-cell interactions result in the polarization of naïve T cells toward IFN-g-producing Th1 cells (34,35).…”

CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity

“…We have previously shown that Cd40 is expressed in FAC-purified ATMs and that obesity and inflammatory signals induce Cd40 expression in ATMs [3]. Given the diverse range of cell types known to express Cd40 in adipose tissue, we used confocal microscopy and flow cytometry analysis to better delineate the expression of CD40 protein in situ.…”

“…Our group is interested in the nature and function of APCs in adipose tissue, and we have found that ATMs are the primary functional APC in fat that promote obesity-induced inflammation [3,4]. Here, we performed an independent evaluation of the importance of CD40 in obesity-induced metainflammation to determine whether CD40/CD0L signaling contributed to ATM-T cell cross talk in obese adipose tissue.…”

“…Adipose tissue inflammation involves activation of both innate and adaptive immune responses [1,2]. MHC class II-restricted signals from macrophages and dendritic cells contribute to T cell activation in response to obesogenic cues and contribute to metabolic dysfunction [3][4][5]. ATMs and dendritic cells can function as APCs and provide critical cues to generate proinflammatory signals that include activation of adipose tissue CD4 + T cells toward a Th1 and effector/memory phenotype [6][7][8].…”