Endoplasmic reticulum aminopeptidase 2 regulates CD4+ T cells pyroptosis in rheumatoid arthritis
Authors' conclusion
Taken together, our results identify a novel mechanism by which ERAP2 regulates RA development and document the effect of the ERAP2/Hedgehog signaling axis on pyroptosis of CD4+ T cells from RA patients.
Study context
- Population
- CD4+ T cells from peripheral venous blood of human subjects with rheumatoid arthritis (RA); chimeric mice engrafted with human synovial tissue and reconstituted with human CD4+ T cells
- Outcome
- Role of ERAP2 in pyroptosis of CD4+ T cells in RA and its molecular mechanism
Methodological detailshuman CD4+ T cells, ERAP2 knockdown and overexpression, chimeric mice engrafted with human synovial tissue
- Human CD4+ T cells
- ERAP2 knockdown and overexpression
- Chimeric mice engrafted with human synovial tissue
Main finding
As reported in the abstract
- CD4+ T cells undergoing pyroptosis elevated in blood and synovium of RA patients
- ERAP2 gene and protein expression significantly higher in CD4+ T cells from RA patients
- ERAP2 deletion suppressed pyroptosis, attenuated Caspase-1 activation in tissue T cells and reduced tissue inflammatory responses
- ERAP2 overexpression triggered inflammasome assembly, activated Caspase-1 and induced pyroptosis in CD4+ T cells
- ERAP2 inhibits the Hedgehog signalling pathway and upregulates NLRP3, cleaved Caspase-1 and Gasdermin D to promote pyroptosis
Original publication
Endoplasmic reticulum aminopeptidase 2 regulates CD4+ T cells pyroptosis in rheumatoid arthritis. Arthritis Res Ther. Published 25 January 2024. doi:10.
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