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Regulation of Orbital Fibrosis and Adipogenesis by Pathogenic Th17 Cells in Graves Orbitopathy
- Source :
- The Journal of clinical endocrinology and metabolism. 102(11)
- Publication Year :
- 2017
-
Abstract
- Context T helper (Th)17 cells are correlated with many human autoimmune disorders, including Graves disease, and may play key roles in the pathogenesis of Graves orbitopathy (GO). Objective To study the phenotype of Th17 cells in patients with GO and healthy subjects, investigate the fibrosis and adipogenesis in orbital fibroblasts (OFs) modulated by interleukin (IL)-17A, and determine the interaction between Th17 cells and OFs. Design/Setting/Participants Blood samples and orbital tissues from GO patients and healthy controls were collected. Main Outcome Measures We conducted multicolor flow cytometry, immunohistochemical and immunofluorescent stainings, Western blotting, a PathScan intracellular signaling assay, Luminex and enzyme-linked immunosorbent assays, and protein mass spectrum. Results Interferon-γ– and IL-22–expressing Th17 cells are increased in GO patients, which are positively related to clinical activity score. Costimulatory molecules are highly expressed in GO orbits and most GO OFs are CD90+. IL-17A promotes TGF-β–induced fibrosis in CD90+ OFs but impedes 15-deoxy-Δ12,14-prostaglandin J2–induced adipogenesis in CD90− OFs. Th17 cells promote proinflammatory cytokine secretion in both CD90+ and CD90− OFs. Meanwhile, both CD90+ and CD90− OFs contribute to Th17 cell differentiation through prostaglandin E2 production, which can be attenuated by indomethacin. Furthermore, Th17 cells upregulate costimulatory molecule expression on OFs. Conclusion Our findings unravel the pathogenicity of IL-17A in the initiation and progression of GO. In-depth interpretation of the molecular basis of OFs delineated by CD90 and Th17–OF interaction will help to afford a novel approach to better therapeutic strategies for GO.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Cellular differentiation
Clinical Biochemistry
030209 endocrinology & metabolism
Context (language use)
Biochemistry
Proinflammatory cytokine
Flow cytometry
03 medical and health sciences
0302 clinical medicine
Endocrinology
Fibrosis
Internal medicine
medicine
Adipocytes
Humans
CD90
Cells, Cultured
Adipogenesis
medicine.diagnostic_test
business.industry
Biochemistry (medical)
Interleukin
Cell Differentiation
Fibroblasts
medicine.disease
Graves Ophthalmopathy
030104 developmental biology
Hyaluronan Receptors
Case-Control Studies
Th17 Cells
business
Orbit
Subjects
Details
- ISSN :
- 19457197
- Volume :
- 102
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Accession number :
- edsair.doi.dedup.....491b8ca1bf13f756a6a0647d34c36beb