CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity

Chao Wang; Nir Yosef; Jellert Gaublomme; Chuan Wu; Youjin Lee; Clary B. Clish; Jim Kaminski; Sheng Xiao; Gerd Meyer Zu Horste; Mathias Pawlak; Yasuhiro Kishi; Nicole Joller; Katarzyna Karwacz; Chen Zhu; Maria Ordovas-Montanes; Asaf Madi; Ivo Wortman; Toru Miyazaki; Raymond A. Sobel; Hongkun Park; Aviv Regev; Vijay K. Kuchroo

doi:10.1016/j.cell.2015.10.068

CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity

Chao Wang, Nir Yosef, Jellert Gaublomme, Chuan Wu, Youjin Lee, Clary B. Clish, Jim Kaminski, Sheng Xiao, Gerd Meyer Zu Horste, Mathias Pawlak, Yasuhiro Kishi, Nicole Joller, Katarzyna Karwacz, Chen Zhu, Maria Ordovas-Montanes, Asaf Madi, Ivo Wortman, Toru Miyazaki, Raymond A. Sobel, Hongkun ParkAviv Regev^*, Vijay K. Kuchroo

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

297 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1413-1427
Number of pages	15
Journal	Cell
Volume	163
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2015.10.068
State	Published - 3 Dec 2015
Externally published	Yes

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Wang, C., Yosef, N., Gaublomme, J., Wu, C., Lee, Y., Clish, C. B., Kaminski, J., Xiao, S., Zu Horste, G. M., Pawlak, M., Kishi, Y., Joller, N., Karwacz, K., Zhu, C., Ordovas-Montanes, M., Madi, A., Wortman, I., Miyazaki, T., Sobel, R. A., ... Kuchroo, V. K. (2015). CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity. Cell, 163(6), 1413-1427. https://doi.org/10.1016/j.cell.2015.10.068

@article{8a22f0368d724eb3afbe45b3f0d40a28,

title = "CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity",

abstract = "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.",

author = "Chao Wang and Nir Yosef and Jellert Gaublomme and Chuan Wu and Youjin Lee and Clish, {Clary B.} and Jim Kaminski and Sheng Xiao and {Zu Horste}, {Gerd Meyer} and Mathias Pawlak and Yasuhiro Kishi and Nicole Joller and Katarzyna Karwacz and Chen Zhu and Maria Ordovas-Montanes and Asaf Madi and Ivo Wortman and Toru Miyazaki and Sobel, {Raymond A.} and Hongkun Park and Aviv Regev and Kuchroo, {Vijay K.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = dec,

day = "3",

doi = "10.1016/j.cell.2015.10.068",

language = "אנגלית",

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Wang, C, Yosef, N, Gaublomme, J, Wu, C, Lee, Y, Clish, CB, Kaminski, J, Xiao, S, Zu Horste, GM, Pawlak, M, Kishi, Y, Joller, N, Karwacz, K, Zhu, C, Ordovas-Montanes, M, Madi, A, Wortman, I, Miyazaki, T, Sobel, RA, Park, H, Regev, A & Kuchroo, VK 2015, 'CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity', Cell, vol. 163, no. 6, pp. 1413-1427. https://doi.org/10.1016/j.cell.2015.10.068

TY - JOUR

T1 - CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity

AU - Wang, Chao

AU - Yosef, Nir

AU - Gaublomme, Jellert

AU - Wu, Chuan

AU - Lee, Youjin

AU - Clish, Clary B.

AU - Kaminski, Jim

AU - Xiao, Sheng

AU - Zu Horste, Gerd Meyer

AU - Pawlak, Mathias

AU - Kishi, Yasuhiro

AU - Joller, Nicole

AU - Karwacz, Katarzyna

AU - Zhu, Chen

AU - Ordovas-Montanes, Maria

AU - Madi, Asaf

AU - Wortman, Ivo

AU - Miyazaki, Toru

AU - Sobel, Raymond A.

AU - Park, Hongkun

AU - Regev, Aviv

AU - Kuchroo, Vijay K.

PY - 2015/12/3

Y1 - 2015/12/3

N2 - 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.

AB - 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.

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VL - 163

SP - 1413

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JO - Cell

JF - Cell

IS - 6

ER -

CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity

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