CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity
نویسندگان
چکیده
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.
منابع مشابه
CD5L/AIM regulates lipid biosythesis and restrains Th17 cell pathogenicity
Chao Wang1, Nir Yosef4,8, Jellert Gaublomme2,3, Chuan Wu1, Youjin Lee1, Clary B. Clish2, Jim Kaminski8, Sheng Xiao1, Gerd Meyer Zu Horste1, Mathias Pawlak1, Yasuhiro Kishi1,9, Nicole Joller1, Katarzyna Karwacz1, Chen Zhu1, Maria Ordovas-Montanes1, Asaf Madi1,2, Ivo Wortman2, Toru Miyazaki6, Raymond A. Sobel5, Hongkun Park2,3, Aviv Regev2,7, and Vijay K. Kuchroo1,2 1Evergrande Center for Immunol...
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ورودعنوان ژورنال:
- Cell
دوره 163 شماره
صفحات -
تاریخ انتشار 2015