DGAT1 inhibits retinol-dependent regulatory T cell formation and mediates autoimmune encephalomyelitis

Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):3126-3135. doi: 10.1073/pnas.1817669116. Epub 2019 Feb 4.


The balance of effector versus regulatory T cells (Tregs) controls inflammation in numerous settings, including multiple sclerosis (MS). Here we show that memory phenotype CD4+ T cells infiltrating the central nervous system during experimental autoimmune encephalomyelitis (EAE), a widely studied animal model of MS, expressed high levels of mRNA for Dgat1 encoding diacylglycerol-O-acyltransferase-1 (DGAT1), an enzyme that catalyzes triglyceride synthesis and retinyl ester formation. DGAT1 inhibition or deficiency attenuated EAE, with associated enhanced Treg frequency; and encephalitogenic, DGAT1-/- in vitro-polarized Th17 cells were poor inducers of EAE in adoptive recipients. DGAT1 acyltransferase activity sequesters retinol in ester form, preventing synthesis of retinoic acid, a cofactor for Treg generation. In cultures with T cell-depleted lymphoid tissues, retinol enhanced Treg induction from DGAT1-/- but not from WT T cells. The WT Treg induction defect was reversed by DGAT1 inhibition. These results demonstrate that DGAT1 suppresses retinol-dependent Treg formation and suggest its potential as a therapeutic target for autoimmune inflammation.

Keywords: T regulatory cell; experimental autoimmune encephalomyelitis; immunometabolism; multiple sclerosis; neuroinflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Central Nervous System
  • Diacylglycerol O-Acyltransferase / genetics*
  • Encephalomyelitis / genetics*
  • Gene Knockout Techniques
  • Humans
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation / pathology
  • Mice
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Tretinoin / metabolism


  • Tretinoin
  • Dgat1 protein, mouse
  • Diacylglycerol O-Acyltransferase