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Hospital","award":["YBKB201901"],"award-info":[{"award-number":["YBKB201901"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-\u03b3t (ROR\u03b3t) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed ROR\u03b3t and Tbet and produced interferon-\u03b3 (IFN-\u03b3). Increased IFN-\u03b3\u2013producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-\u03b3\u2013producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa124","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T04:27:34Z","timestamp":1584332854000},"page":"1851-1867","source":"Crossref","is-referenced-by-count":41,"title":["Evidence for Associations Between Th1\/Th17 \u201cHybrid\u201d Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1423-4820","authenticated-orcid":false,"given":"Sijie","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shanghai Ninth People\u2019s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China"},{"name":"Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China"},{"name":"Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China"},{"name":"Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai Ninth People\u2019s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China"},{"name":"Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China"},{"name":"Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China"},{"name":"Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhuo","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai Ninth People\u2019s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China"},{"name":"Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China"},{"name":"Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China"},{"name":"Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of 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