Evidence for associations between Th1/Th17 "hybrid" phenotype and altered lipometabolism in very severe Graves' orbitopathy.

Evidence for associations between Th1/Th17 "hybrid" phenotype and altered lipometabolism in very severe Graves' orbitopathy.:

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Evidence for associations between Th1/Th17 "hybrid" phenotype and altered lipometabolism in very severe Graves' orbitopathy.

J Clin Endocrinol Metab. 2020 Mar 16;:

Authors: Fang S, Zhang S, Huang Y, Wu Y, Lu Y, Zhong S, Liu X, Wang Y, Li Y, Sun J, Gu P, Zhou H, Fan X

Abstract

PURPOSE: To investigate the characteristics of Th1 and Th17 cell lineages for very severe Graves' orbitopathy (GO) development.

METHODS: 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 sera from very severe GO patients before and after glucocorticoids (GCs) therapy. Immunohistochemistry and western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization.

RESULTS: In GD, Th1 cells predominated in peripheral effector T cell subsets while in GO, Th17 lineages predominated. In moderate-to-severe GO, Th17.1 cells expressed RORγt independently and produced IL-17A while in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced IFN-γ. Increased IFN-γ-producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GCs therapy inhibited both Th1 and Th17 lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GCs resistant very severe GO, IFN-γ-producing Th17.1 cells were still at a high level, correlating with increased serum triglycerides. Further, retroorbital tissues from GCs 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.

CONCLUSIONS: 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.

PMID: 32173759 [PubMed - as supplied by publisher]