DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture

Abnormal immune response of the body against substances and tissues causes autoimmune diseases, such as polymyositis, dermatomyositis, and rheumatoid arthritis. Irregular lipid metabolism and inflammation may be a significant cause of autoimmune diseases. Although much progress has been made, mechan...

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Main Authors: Qi-bing Xie, Yan Liang, Min Yang, Yuan Yang, Xiao-min Cen, Geng Yin
Format: Article
Language:English
Published: Hindawi Limited 2017-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2017/5252840
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spelling doaj-05e10ee38a7c416593c1e4d46e6619852020-11-25T01:43:17ZengHindawi LimitedJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/52528405252840DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC CultureQi-bing Xie0Yan Liang1Min Yang2Yuan Yang3Xiao-min Cen4Geng Yin5Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, ChinaDepartment of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, ChinaDepartment of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, ChinaDepartment of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, ChinaDepartment of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, ChinaDepartment of General Practice, West China Hospital of Sichuan University, Chengdu 610041, ChinaAbnormal immune response of the body against substances and tissues causes autoimmune diseases, such as polymyositis, dermatomyositis, and rheumatoid arthritis. Irregular lipid metabolism and inflammation may be a significant cause of autoimmune diseases. Although much progress has been made, mechanisms of initiation and proceeding of metabolic and inflammatory regulation in autoimmune disease have not been well-defined. And novel markers for the detection and therapy of autoimmune disease are urgent. mTOR signaling is a central regulator of extracellular metabolic and inflammatory processes, while DEP domain-containing mTOR-interacting protein (DEPTOR) is a natural inhibitor of mTOR. Here, we report that overexpression of DEPTOR reduces mTORC1 activity in lymphocytes of human peripheral blood mononuclear cells (PBMCs). Combination of DEPTOR overexpression and mTORC2/AKT inhibitors effectively inhibits lipogenesis and inflammation in lymphocytes of PBMC culture. Moreover, DEPTOR knockdown activates mTORC1 and increases lipogenesis and inflammations. Our findings provide a deep insight into the relationship between lipid metabolism and inflammations via DEPTOR-mTOR pathway and imply that DEPTOR-mTOR in lymphocytes of PBMC culture has the potential to be as biomarkers for the detection and therapies of autoimmune diseases.http://dx.doi.org/10.1155/2017/5252840
collection DOAJ
language English
format Article
sources DOAJ
author Qi-bing Xie
Yan Liang
Min Yang
Yuan Yang
Xiao-min Cen
Geng Yin
spellingShingle Qi-bing Xie
Yan Liang
Min Yang
Yuan Yang
Xiao-min Cen
Geng Yin
DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture
Journal of Immunology Research
author_facet Qi-bing Xie
Yan Liang
Min Yang
Yuan Yang
Xiao-min Cen
Geng Yin
author_sort Qi-bing Xie
title DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture
title_short DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture
title_full DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture
title_fullStr DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture
title_full_unstemmed DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture
title_sort deptor-mtor signaling is critical for lipid metabolism and inflammation homeostasis of lymphocytes in human pbmc culture
publisher Hindawi Limited
series Journal of Immunology Research
issn 2314-8861
2314-7156
publishDate 2017-01-01
description Abnormal immune response of the body against substances and tissues causes autoimmune diseases, such as polymyositis, dermatomyositis, and rheumatoid arthritis. Irregular lipid metabolism and inflammation may be a significant cause of autoimmune diseases. Although much progress has been made, mechanisms of initiation and proceeding of metabolic and inflammatory regulation in autoimmune disease have not been well-defined. And novel markers for the detection and therapy of autoimmune disease are urgent. mTOR signaling is a central regulator of extracellular metabolic and inflammatory processes, while DEP domain-containing mTOR-interacting protein (DEPTOR) is a natural inhibitor of mTOR. Here, we report that overexpression of DEPTOR reduces mTORC1 activity in lymphocytes of human peripheral blood mononuclear cells (PBMCs). Combination of DEPTOR overexpression and mTORC2/AKT inhibitors effectively inhibits lipogenesis and inflammation in lymphocytes of PBMC culture. Moreover, DEPTOR knockdown activates mTORC1 and increases lipogenesis and inflammations. Our findings provide a deep insight into the relationship between lipid metabolism and inflammations via DEPTOR-mTOR pathway and imply that DEPTOR-mTOR in lymphocytes of PBMC culture has the potential to be as biomarkers for the detection and therapies of autoimmune diseases.
url http://dx.doi.org/10.1155/2017/5252840
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