title: DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture.
abstract: 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.
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Qi-Bing
authors.identifier: 0000-0001-6830-8026
authors.initials: QB
authors.lastname: Xie
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Min
authors.identifier: 0000-0003-2444-4194
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Xiao-Min
authors.identifier: 0000-0001-9000-4141
authors.initials: XM
authors.lastname: Cen
authors.affiliation: Department of General Practice, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Geng
authors.identifier: 0000-0002-1336-9072
authors.initials: G
authors.lastname: Yin
mesh_terms: D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D000076225:Mechanistic Target of Rapamycin Complex 2; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; C556139:DEPTOR protein, human; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases