CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity
Th17 cells play a critical role in host defense against extracellular pathogens and tissue homeostasis, but can induce autoimmunity. The mechanisms implicated in balancing ‘pathogenic’ and ‘non-pathogenic’ Th17 cell states remain largely unknown. We used single-cell RNA-seq to identify CD5L/AIM as...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2016
|
| Online Access: | http://hdl.handle.net/1721.1/105772 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826216996841193472 |
|---|---|
| author | Wang, Chao Yosef, Nir Gaublomme, Jellert Wu, Chuan Lee, Youjin Clish, Clary B. Kaminski, Jim Xiao, Sheng Zu Horste, Gerd Meyer Pawlak, Mathias Kishi, Yasuhiro Joller, Nicole Karwacz, Katarzyna Zhu, Chen Ordovas-Montanes, Maria Madi, Asaf Wortman, Ivo Miyazaki, Toru Sobel, Raymond A. Park, Hongkun Regev, Aviv Kuchroo, Vijay K. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Wang, Chao Yosef, Nir Gaublomme, Jellert Wu, Chuan Lee, Youjin Clish, Clary B. Kaminski, Jim Xiao, Sheng Zu Horste, Gerd Meyer Pawlak, Mathias Kishi, Yasuhiro Joller, Nicole Karwacz, Katarzyna Zhu, Chen Ordovas-Montanes, Maria Madi, Asaf Wortman, Ivo Miyazaki, Toru Sobel, Raymond A. Park, Hongkun Regev, Aviv Kuchroo, Vijay K. |
| author_sort | Wang, Chao |
| collection | MIT |
| description | Th17 cells play a critical role in host defense against extracellular pathogens and tissue homeostasis, but can induce autoimmunity. The mechanisms implicated in balancing ‘pathogenic’ and ‘non-pathogenic’ Th17 cell states remain largely unknown. We used single-cell RNA-seq to
identify CD5L/AIM as a regulator expressed in ‘non-pathogenic’ but not in ‘pathogenic’ Th17 cells. Although CD5L does not affect Th17 differentiation, it is a functional switch that regulates the pathogenicity of Th17 cells. Loss of CD5L converts ‘non-pathogenic’ Th17 cells into
‘pathogenic’ cells that induce autoimmunity. CD5L mediates this effect by modulating the intracellular lipidome, altering fatty acid composition, and restricting cholesterol biosynthesis, and thus ligand availability for Rorγt, the master transcription factor of Th17 cells. Our study identifies
CD5L as a critical regulator of the Th17 cell functional state and highlights the importance of lipid metabolism in balancing immune protection and disease induced by T cells. |
| first_indexed | 2024-09-23T16:56:24Z |
| format | Article |
| id | mit-1721.1/105772 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:56:24Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1057722022-10-03T09:17:29Z CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity Wang, Chao Yosef, Nir Gaublomme, Jellert Wu, Chuan Lee, Youjin Clish, Clary B. Kaminski, Jim Xiao, Sheng Zu Horste, Gerd Meyer Pawlak, Mathias Kishi, Yasuhiro Joller, Nicole Karwacz, Katarzyna Zhu, Chen Ordovas-Montanes, Maria Madi, Asaf Wortman, Ivo Miyazaki, Toru Sobel, Raymond A. Park, Hongkun Regev, Aviv Kuchroo, Vijay K. Massachusetts Institute of Technology. Department of Biology Regev, Aviv Th17 cells play a critical role in host defense against extracellular pathogens and tissue homeostasis, but can induce autoimmunity. The mechanisms implicated in balancing ‘pathogenic’ and ‘non-pathogenic’ Th17 cell states remain largely unknown. We used single-cell RNA-seq to identify CD5L/AIM as a regulator expressed in ‘non-pathogenic’ but not in ‘pathogenic’ Th17 cells. Although CD5L does not affect Th17 differentiation, it is a functional switch that regulates the pathogenicity of Th17 cells. Loss of CD5L converts ‘non-pathogenic’ Th17 cells into ‘pathogenic’ cells that induce autoimmunity. CD5L mediates this effect by modulating the intracellular lipidome, altering fatty acid composition, and restricting cholesterol biosynthesis, and thus ligand availability for Rorγt, the master transcription factor of Th17 cells. Our study identifies CD5L as a critical regulator of the Th17 cell functional state and highlights the importance of lipid metabolism in balancing immune protection and disease induced by T cells. Klarman Cell Observatory Howard Hughes Medical Institute National Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Grant P30-CA14051) 2016-12-09T15:42:32Z 2016-12-09T15:42:32Z 2015-11 2015-08 Article http://purl.org/eprint/type/JournalArticle 00928674 http://hdl.handle.net/1721.1/105772 Wang, Chao et al. “CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity.” Cell 163.6 (2015): 1413–1427. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1016/j.cell.2015.10.068 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Wang, Chao Yosef, Nir Gaublomme, Jellert Wu, Chuan Lee, Youjin Clish, Clary B. Kaminski, Jim Xiao, Sheng Zu Horste, Gerd Meyer Pawlak, Mathias Kishi, Yasuhiro Joller, Nicole Karwacz, Katarzyna Zhu, Chen Ordovas-Montanes, Maria Madi, Asaf Wortman, Ivo Miyazaki, Toru Sobel, Raymond A. Park, Hongkun Regev, Aviv Kuchroo, Vijay K. CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity |
| title | CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity |
| title_full | CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity |
| title_fullStr | CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity |
| title_full_unstemmed | CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity |
| title_short | CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity |
| title_sort | cd5l aim regulates lipid biosynthesis and restrains th17 cell pathogenicity |
| url | http://hdl.handle.net/1721.1/105772 https://orcid.org/0000-0001-8567-2049 |
| work_keys_str_mv | AT wangchao cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT yosefnir cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT gaublommejellert cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT wuchuan cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT leeyoujin cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT clishclaryb cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT kaminskijim cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT xiaosheng cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT zuhorstegerdmeyer cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT pawlakmathias cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT kishiyasuhiro cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT jollernicole cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT karwaczkatarzyna cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT zhuchen cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT ordovasmontanesmaria cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT madiasaf cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT wortmanivo cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT miyazakitoru cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT sobelraymonda cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT parkhongkun cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT regevaviv cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity AT kuchroovijayk cd5laimregulateslipidbiosynthesisandrestrainsth17cellpathogenicity |