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Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
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Celastrol ameliorates experimental autoimmune uveitis through STAT3 targeting and gut microenvironment reprofiling
Shengjin Xiang1, Jinrun Chen2, Mengyun Deng2
1National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
International Immunopharmacology
|December 8, 2023
Summary
Celastrol (CEL) effectively treats autoimmune uveitis by targeting the STAT3-IL17 pathway and modulating the gut microbiome. This research highlights CEL
Area of Science:
- Immunology
- Ophthalmology
- Microbiome Research
Background:
- Celastrol (CEL) shows therapeutic potential in various diseases.
- Its role in autoimmune uveitis has not been previously investigated.
Purpose of the Study:
- To investigate the prophylactic and therapeutic effects of CEL on experimental autoimmune uveitis (EAU).
- To elucidate the underlying mechanisms, including molecular targets and gut microbiome alterations.
Main Methods:
- Utilized a rat experimental autoimmune uveitis model.
- Employed network pharmacology, functional enrichment, and molecular docking for target prediction.
- Validated effects using clinical and histopathological assessments, and molecular assays.
- Analyzed gut microbiome and metabolome using 16S rRNA sequencing and untargeted metabolomics.
Main Results:
- CEL suppressed TH17 responses, inhibited inflammatory cell migration, and preserved the blood-retinal barrier (BRB) integrity by targeting the STAT3-IL17 pathway.
- CEL altered gut microbiota composition, reducing opportunistic pathogens and increasing beneficial bacteria.
- CEL modulated gut metabolites, affecting bile acids, steroids, and other compounds.
Conclusions:
- CEL ameliorates experimental autoimmune uveitis through dual mechanisms.
- These mechanisms involve targeting the STAT3 pathway and reprogramming the gut microenvironment.
