Lipid Rafts & Co.: An integrated model of membrane organization in T cell activation
Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. Progress in Lipid Research
(Impact Factor: 10.02).
06/2006; 45(3):187-202. DOI: 10.1016/j.plipres.2006.01.002
The model of membrane compartmentalization by self-organizing functional lipid microdomains, named lipid rafts, has been a fruitful concept resulting in great progress in understanding T cell signal transduction. However, due to recent results it has become clear that lipid rafts describe only one out of several membrane organizing principles crucial for T cell activation besides fences and pickets and protein-protein interactions that take part in the formation of the immunological synapse as a highly organized structure at the T cell contact site to the antigen-presenting cell. This review describes the concepts of lipid rafts and other membrane organizing principles to evolve a novel integrated model on the functional role of microdomains in immunological synapse formation and T cell activation. Further research has to elucidate the relative contribution and interrelation of different modes of membrane organization in productive T cell activation.
Available from: Giuseppe Danilo Norata
- "The function of the lipid raft is correlated to its cholesterol content and the removal of cholesterol from these micro-domains can interfere with signaling pathways in immune cells, and with antigen-presenting function. One main function of lipid rafts is the regulation of signaling through the T cell receptors.– As an example, the localization of major histocompatibility (MHC) class II molecules in lipid rafts– facilitate the function of antigen-presenting cells and is essential for T cell activation, as this process decreases the amount of antigen necessary for T cell activation., "
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ABSTRACT: High density lipoproteins (HDL) promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. This ability is responsible for the most relevant anti-atherogenic effect of HDL. The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes. Furthermore, during inflammation, the composition of this class of lipoproteins varies to a large extent, thus promoting the formation of dysfunctional HDL. The aim of this review is to discuss the emerging role of HDL in modulating the activity of immune cells and immune-inflammatory mediators during atherogenesis.
Available from: Yap-Seng Chong
- "Incorporation of PUFAs into antigen-presenting cells has been reported to downregulate their function and alter recognition by T cells . EPA and DHA incorporate into lymphocyte membranes and alter the fluidity, suppress signal transduction and affect T-cell proliferation . Furthermore, it has been shown to change the protein composition of the inner membrane lipid leaflet resulting in inhibition of T-cell responses and activation-induced cell death [55, 56]. "
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ABSTRACT: Maternal nutrition has critical effects on the developing structures and functions of the fetus. Malnutrition during pregnancy can result in low birth weight and small for gestational age babies, increase risk for infection, and impact the immune system. Long-chain polyunsaturated fatty acids (PUFAs) have been reported to have immunomodulatory effects. Decreased consumption of omega-6 PUFAs, in favor of more anti-inflammatory omega-3 PUFAs in modern diets, has demonstrated the potential protective role of omega-3 PUFAs in allergic and respiratory diseases. In this paper, we examine the role of PUFAs consumption during pregnancy and early childhood and its influence on allergy and respiratory diseases. PUFAs act via several mechanisms to modulate immune function. Omega-3 PUFAs may alter the T helper (Th) cell balance by inhibiting cytokine production which in turn inhibits immunoglobulin E synthesis and Th type 2 cell differentiation. PUFAs may further modify cellular membrane, induce eicosanoid metabolism, and alter gene expression. These studies indicate the benefits of omega-3 PUFAs supplementation. Nevertheless, further investigations are warranted to assess the long-term effects of omega-3 PUFAs in preventing other immune-mediated diseases, as well as its effects on the later immunodefense and health status during early growth and development.
Available from: Teodor-Doru Brumeanu
- "Cholesterol-rich microdomains known as lipid rafts are postulated to be a driving force in immunological synapse formation and critical for T-cell signaling , –. "
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ABSTRACT: Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40–50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4+
Foxp3+ T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response.
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