CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity.

Cell
Authors
Keywords
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.

Year of Publication
2015
Journal
Cell
Volume
163
Issue
6
Pages
1413-27
Date Published
2015 Dec 03
ISSN
1097-4172
URL
DOI
10.1016/j.cell.2015.10.068
PubMed ID
26607793
PubMed Central ID
PMC4671820
Links
Grant list
R01 NS030843 / NS / NINDS NIH HHS / United States
R00 AI110649 / AI / NIAID NIH HHS / United States
NS030843 / NS / NINDS NIH HHS / United States
AI039671 / AI / NIAID NIH HHS / United States
P01 AI056299 / AI / NIAID NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
P01 NS076410 / NS / NINDS NIH HHS / United States
P01 AI039671 / AI / NIAID NIH HHS / United States
Howard Hughes Medical Institute / United States
R37 NS030843 / NS / NINDS NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
P01 AI045757 / AI / NIAID NIH HHS / United States
4R00AI110649 / AI / NIAID NIH HHS / United States
AI056299 / AI / NIAID NIH HHS / United States
R29 NS030843 / NS / NINDS NIH HHS / United States
NS076410 / NS / NINDS NIH HHS / United States