2. Academic Validation
  3. Oleic acid availability impacts thymocyte preprogramming and subsequent peripheral Treg cell differentiation

Oleic acid availability impacts thymocyte preprogramming and subsequent peripheral Treg cell differentiation

  • Nat Immunol. 2023 Dec 7. doi: 10.1038/s41590-023-01672-1.
Liangyu Lin # 1,  Mingyuan Hu # 1,  Qing Li 1,  Liming Du 1,  Li Lin 2,  Yueqing Xue 1,  Fanjun Zheng 1,  Fei Wang 1,  Keli Liu 2,  Yu Wang 1,  Jiayin Ye 1,  Xu Jiang 1,  Xuefeng Wang 1,  Jiaqi Wang 1,  Jingjie Zhai 1,  Benming Liu 1,  Hongzhen Xie 1,  Yanqin You 3,  Jinyong Wang 4,  Xiangyin Kong 1,  Dechun Feng 1,  Douglas R Green 5,  Yufang Shi 6 7,  Ying Wang 8
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 2 School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 3 Department of Obstetrics and Gynecology, First Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 4 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
  • 5 Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • 6 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. yfshi@suda.edu.cn.
  • 7 The Third Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, Suzhou, China. yfshi@suda.edu.cn.
  • 8 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. yingwang@sibs.ac.cn.
  • # Contributed equally.
PMID: 38062135 DOI: 10.1038/s41590-023-01672-1
Abstract

The nature of activation signals is essential in determining T cell subset differentiation; however, the features that determine T cell subset preference acquired during intrathymic development remain elusive. Here we show that naive CD4+ T cells generated in the mouse thymic microenvironment lacking Scd1, encoding the Enzyme catalyzing oleic acid (OA) production, exhibit enhanced regulatory T (Treg) cell differentiation and attenuated development of experimental autoimmune encephalomyelitis. Scd1 deletion in K14+ thymic epithelia recapitulated the enhanced Treg cell differentiation phenotype of Scd1-deficient mice. The dearth of OA permitted DOT1L to increase H3K79me2 levels at the Atp2a2 locus of thymocytes at the DN2-DN3 transition stage. Such epigenetic modification persisted in naive CD4+ T cells and facilitated Atp2a2 expression. Upon T cell receptor activation, ATP2A2 enhanced the activity of the calcium-NFAT1-Foxp3 axis to promote naive CD4+ T cells to differentiate into Treg cells. Therefore, OA availability is critical for preprogramming thymocytes with Treg cell differentiation propensities in the periphery.

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