Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response.
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. Enri...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3378591?pdf=render |
| _version_ | 1811218708598620160 |
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| author | Jacqueline Surls Cristina Nazarov-Stoica Margaret Kehl Cara Olsen Sofia Casares Teodor-D Brumeanu |
| author_facet | Jacqueline Surls Cristina Nazarov-Stoica Margaret Kehl Cara Olsen Sofia Casares Teodor-D Brumeanu |
| author_sort | Jacqueline Surls |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T07:13:56Z |
| format | Article |
| id | doaj.art-77aa4cc9ba23459da0260ca447f65535 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T07:13:56Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-77aa4cc9ba23459da0260ca447f655352022-12-22T03:42:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3873310.1371/journal.pone.0038733Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response.Jacqueline SurlsCristina Nazarov-StoicaMargaret KehlCara OlsenSofia CasaresTeodor-D BrumeanuCell 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.http://europepmc.org/articles/PMC3378591?pdf=render |
| spellingShingle | Jacqueline Surls Cristina Nazarov-Stoica Margaret Kehl Cara Olsen Sofia Casares Teodor-D Brumeanu Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response. PLoS ONE |
| title | Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response. |
| title_full | Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response. |
| title_fullStr | Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response. |
| title_full_unstemmed | Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response. |
| title_short | Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response. |
| title_sort | increased membrane cholesterol in lymphocytes diverts t cells toward an inflammatory response |
| url | http://europepmc.org/articles/PMC3378591?pdf=render |
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