Authors:	Hai, Yuanping
Title:	Immunohistochemistry study in human orbital tissue of thyroid eye disease
Online publication date:	7-Jul-2022
Year of first publication:	2022
Language:	english
Abstract:	Thyroid eye disease (TED) is an orbital inflammatory disease. The current management is suboptimal because of unclear mechanisms. Many in vitro studies have confirmed that the pathogenesis involves several pathogenic pathways and a network of infiltrating mononuclear cells, cytokines, and chemokines in the orbit. However, the in vivo environment is sometimes different from the in vitro situation. Orbital tissue is the best sample to reflect local inflammation. Additionally, immunohistochemistry (IHC) analysis of orbital tissue can reveal the local orbital immunity and correlate the microscopic changes with the macroscopic clinical features. Several IHC studies have been performed in TED but with several limitations, and the pathogenesis of some molecules remains unclear. Uncovering the molecular mechanism that plays a significant role in TED may help develop novel therapeutic strategies and optimize the management of TED. In this study, we carried out staining of a large number of orbital tissue samples from patients with well-documented demographic and clinical data using antibodies against 18 proteins involved in multiple pathways that contribute to the pathogenesis of TED, and then investigated the primary mechanism. This study found that TSHR and IGF-1R signaling played a vital role in the pathogenesis of TED by activating pathways that resulted in the enhanced activation of orbital fibroblasts. T cells (CD3) and macrophages (CD68) were the main infiltrating immunocytes in the inflammatory stage of TED. IL-17A stimulated the differentiation of orbital fibroblasts into pre-adipocytes and myofibroblasts, and IL-17A, IL-23A, and IL-6 stimulated orbital fibroblasts to secrete hydrophilic hyaluronan and glycosaminoglycans. Furthermore, RANTES attracted T cells to migrate into the orbit, and MCP-1 promoted monocyte/macrophage migration into orbit. BAFF might participate in the primary mechanism by promoting B cell survival and maturation. The CD40-CD40L pathway is involved in the inflammatory response by mediating the interaction between orbital fibroblasts and T cells. Targeting these key players may provide more effective and disease-specific treatment strategies.
DDC:	600 Technik 600 Technology (Applied sciences) 610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 09 Chemie, Pharmazie u. Geowissensch.
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7263
URN:	urn:nbn:de:hebis:77-openscience-854bcc80-7019-4866-802a-de88ba992df33
Version:	Original work
Publication type:	Dissertation
License:	In Copyright
Information on rights of use:	http://rightsstatements.org/vocab/InC/1.0/
Extent:	VIII, 78 Seiten, Illustrationen, Diagramme
Appears in collections:	JGU-Publikationen