Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity
Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q.
Rockefeller University Press
Published 2018
Rockefeller University Press
Published 2018
| Publication Date: |
2018-06-05
|
|---|---|
| Publisher: |
Rockefeller University Press
|
| Print ISSN: |
0022-1007
|
| Electronic ISSN: |
1540-9538
|
| Topics: |
Medicine
|
| Keywords: |
Tumor Immunology, Metabolism
|
| Published by: |
| _version_ | 1836398959488139264 |
|---|---|
| autor | Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. |
| beschreibung | CD8 + T cells can be polarized into IL-9–secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. |
| citation_standardnr | 6276244 |
| datenlieferant | ipn_articles |
| feed_id | 96 |
| feed_publisher | Rockefeller University Press |
| feed_publisher_url | http://www.rupress.org/ |
| insertion_date | 2018-06-05 |
| journaleissn | 1540-9538 |
| journalissn | 0022-1007 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | Rockefeller University Press |
| quelle | Journal of Experimental Medicine |
| relation | http://jem.rupress.org/cgi/content/short/215/6/1555?rss=1 |
| schlagwort | Tumor Immunology, Metabolism |
| search_space | articles |
| shingle_author_1 | Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. |
| shingle_author_2 | Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. |
| shingle_author_3 | Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. |
| shingle_author_4 | Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. |
| shingle_catch_all_1 | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity Tumor Immunology, Metabolism CD8 + T cells can be polarized into IL-9–secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_2 | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity Tumor Immunology, Metabolism CD8 + T cells can be polarized into IL-9–secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_3 | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity Tumor Immunology, Metabolism CD8 + T cells can be polarized into IL-9–secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_4 | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity Tumor Immunology, Metabolism CD8 + T cells can be polarized into IL-9–secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. Ma, X., Bi, E., Huang, C., Lu, Y., Xue, G., Guo, X., Wang, A., Yang, M., Qian, J., Dong, C., Yi, Q. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_title_1 | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity |
| shingle_title_2 | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity |
| shingle_title_3 | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity |
| shingle_title_4 | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity |
| timestamp | 2025-06-30T23:35:19.981Z |
| titel | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity |
| titel_suche | Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity |
| topic | WW-YZ |
| uid | ipn_articles_6276244 |