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

Research output: Contribution to journalArticlepeer-review


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 Rorgt, 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 languageEnglish
Pages (from-to)1413-1427
Number of pages15
Issue number6
Early online date19 Nov 2015
StatePublished - 3 Dec 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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