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- W1971949641 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." @default.
- W1971949641 created "2016-06-24" @default.
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- W1971949641 creator A5069197438 @default.
- W1971949641 date "2012-06-19" @default.
- W1971949641 modified "2023-10-02" @default.
- W1971949641 title "Increased Membrane Cholesterol in Lymphocytes Diverts T-Cells toward an Inflammatory Response" @default.
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- W1971949641 doi "https://doi.org/10.1371/journal.pone.0038733" @default.
- W1971949641 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3378591" @default.
- W1971949641 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22723880" @default.
- W1971949641 hasPublicationYear "2012" @default.
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