PMID- 32201095 OWN - NLM STAT- MEDLINE DCOM- 20210806 LR - 20211204 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 225 IP - 3 DP - 2020 May TI - The mTOR-glycolytic pathway promotes T-cell immunobiology in oral lichen planus. PG - 151933 LID - S0171-2985(20)30004-8 [pii] LID - 10.1016/j.imbio.2020.151933 [doi] AB - Oral lichen planus (OLP) is a T-cell-mediated inflammatory mucosal disease. T cells require rapid metabolic reprogramming for their effector functions after activation by immunologic stimuli. The mammalian target of rapamycin (mTOR) is a central player in the metabolic reprogramming and immune responses of T cells. The present study investigated the role of mTOR in the immunometabolism of OLP. mTOR and its direct target eukaryotic initiation factor 4E binding protein 1 (4E-BP1) were highly phosphorylated in peripheral T cells of OLP patients. Rapamycin-mediated blockage of mTOR activation restrained both T-cell proliferation and DNA synthesis, promoted apoptosis, and decreased Th1/Th2 and Th17/Treg ratios. Dual blockage of mTOR and phosphatidylinositol 3-kinase (PI3K) exerted stronger inhibition on T-cell immunobiology than selective repression of PI3K alone. Rapamycin also blocked the glycolytic pathway in T cells. Moreover, glucose-induced activation of mTOR-glycolytic pathway increased T-cell proliferation, DNA synthesis, and the Th17/Treg ratio, and decreased T-cell apoptosis. In contrast, inhibition of glycolysis by 2-Deoxy-d-glucose (2-DG) yielded the opposite effects on T-cell immunobiology by blocking the mTOR pathway. In conclusion, enhanced activation of the mTOR-glycolytic pathway promoted T-cell immunobiology, suggesting that dysregulation of immunometabolism might be associated with T-cell dysfunction in OLP. CI - Copyright (c) 2020 Elsevier GmbH. All rights reserved. FAU - Wang, Fang AU - Wang F AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China. FAU - Zhang, Jing AU - Zhang J AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China; Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, China. FAU - Zhou, Gang AU - Zhou G AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, China; Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, China. Electronic address: zhougang@whu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200309 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Apoptosis/immunology MH - *Disease Susceptibility MH - Energy Metabolism MH - Glucose/metabolism MH - Glycolysis MH - Lichen Planus, Oral/*etiology/*metabolism/pathology MH - Lymphocyte Activation/immunology MH - Phosphatidylinositol 3-Kinases/metabolism MH - *Signal Transduction MH - T-Lymphocytes/*immunology/*metabolism MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - 2-DG OT - Glucose OT - Glycolysis OT - Immunometabolism OT - PI3K OT - Rapamycin COIS- Declaration of Competing Interest All authors declared no conflict of interest. EDAT- 2020/03/24 06:00 MHDA- 2021/08/07 06:00 CRDT- 2020/03/24 06:00 PHST- 2020/01/07 00:00 [received] PHST- 2020/03/05 00:00 [revised] PHST- 2020/03/07 00:00 [accepted] PHST- 2020/03/24 06:00 [pubmed] PHST- 2021/08/07 06:00 [medline] PHST- 2020/03/24 06:00 [entrez] AID - S0171-2985(20)30004-8 [pii] AID - 10.1016/j.imbio.2020.151933 [doi] PST - ppublish SO - Immunobiology. 2020 May;225(3):151933. doi: 10.1016/j.imbio.2020.151933. Epub 2020 Mar 9.