美国圣犹大儿童研究医院Hongbo Chi研究小组发现，蛋白质异戊二烯化调控效应T_reg细胞的分化和维持。这一研究成果于2020年11月17日在线发表在国际学术期刊《细胞—代谢》上。

Title: Protein Prenylation Drives Discrete Signaling Programs for the Differentiation and Maintenance of Effector Treg Cells

Author: Wei Su, Nicole M. Chapman, Jun Wei, Hu Zeng, Yogesh Dhungana, Hao Shi, Jordy Saravia, Peipei Zhou, Lingyun Long, Sherri Rankin, Anil KC, Peter Vogel, Hongbo Chi

Issue&Volume: 2020-11-17

Abstract: Effector regulatory T (eTreg) cells are essential for immune tolerance and depend upon T cell receptor (TCR) signalsfor generation. The immunometabolic signaling mechanisms that promote the differentiationand maintenance of eTreg cells remain unclear. Here, we show that isoprenoid-dependent posttranslational lipidmodifications dictate eTreg cell accumulation and function by intersecting with TCR-induced intracellular signaling.We find that isoprenoids are essential for activated Treg cell suppressive activity, and Treg cell-specific deletion of the respective farnesylation- and geranylgeranylation-promotingenzymes Fntb or Pggt1b leads to the development of fatal autoimmunity, associatedwith reduced eTreg cell accumulation. Mechanistically, Fntb promotes eTreg cell maintenance by regulating mTORC1 activity and ICOS expression. In contrast,Pggt1b acts as a rheostat of TCR-dependent transcriptional programming and Rac-mediatedsignaling for establishment of eTreg cell differentiation and immune tolerance. Therefore, our results identify bidirectionalmetabolic signaling, specifically between immunoreceptor signaling and metabolism-mediatedposttranslational lipid modifications, for the differentiation and maintenance ofeTreg cells.

DOI: 10.1016/j.cmet.2020.10.022

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30591-X