학술논문
1-Oleoyl-lysophosphatidylethanolamine stimulates RORγt activity in T H 17 cells.
Document Type
Academic Journal
Author
Endo Y; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Department of Omics Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana. Chuo-ku, Chiba 260-8670 Japan.; AMED-CREST, AMED, Tokyo, Japan.; Kanno T; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Nakajima T; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Ikeda K; Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Taketomi Y; Laboratory of Microenvironmental Metabolic Health Sciences Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 Japan.; Yokoyama S; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Sasamoto S; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Asou HK; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Miyako K; Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Hasegawa Y; Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Kawashima Y; Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Ohara O; Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan.; Murakami M; AMED-CREST, AMED, Tokyo, Japan.; Laboratory of Microenvironmental Metabolic Health Sciences Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 Japan.; Nakayama T; AMED-CREST, AMED, Tokyo, Japan.; Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana. Chuo-ku, Chiba 260-8670 Japan.
Source
Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE
Subject
Language
English
Abstract
Metabolic fluxes involving fatty acid biosynthesis play essential roles in controlling the differentiation of T helper 17 (T H 17) cells. However, the exact enzymes and lipid metabolites involved, as well as their link to promoting the core gene transcriptional signature required for the differentiation of T H 17 cells, remain largely unknown. From a pooled CRISPR-based screen and unbiased lipidomics analyses, we identified that 1-oleoyl-lysophosphatidylethanolamine could act as a lipid modulator of retinoid-related orphan receptor gamma t (RORγt) activity in T H 17 cells. In addition, we specified five enzymes, including Gpam , Gpat3 , Lplat1 , Pla2g12a , and Scd2 , suggestive of the requirement of glycerophospholipids with monounsaturated fatty acids being required for the transcription of Il17a . 1-Oleoyl-lysophosphatidylethanolamine was reduced in Pla2g12a -deficient T H 17 cells, leading to the abolition of interleukin-17 (IL-17) production and disruption to the core transcriptional program required for the differentiation of T H 17 cells. Furthermore, mice with T cell-specific deficiency of Pla2g12a failed to develop disease in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Thus, our data indicate that 1-oleoyl-lysophosphatidylethanolamine is a lipid metabolite that promotes RORγt-induced T H 17 cell differentiation and the pathogenicity of T H 17 cells.