Mitochondrial Control of Proteasomal Psmb5 Drives the Differentiation of Tissue‐Resident Memory T Cells in Patients with Rheumatoid Arthritis
Authors' conclusion
Mitochondrial succinyl-CoA fosters the succinylation of BRD2, resulting in compromised transcription of proteasomal Psmb5 and the differentiation of Trm cells in RA.
Study context
- Population
- Patients with rheumatoid arthritis (RA) and healthy individuals; humanized NSG chimeras representing synovitis
- Comparison
- RA patients vs healthy individuals
Methodological detailstargeted silencing experiments, ChIP-qPCR, humanized NSG chimeras representing synovitis
- Targeted silencing experiments
- ChIP-qPCR
- Humanized NSG chimeras representing synovitis
Main finding
As reported in the abstract
- In RA, CD4+ T cells notably predisposed to differentiate into Trm cells, positively correlated with DAS28
- Hobit a pivotal facilitator of RA CD4+ Trm cell formation
- Dysregulated proteasomal Psmb5 in RA T cells the key factor in elevated Hobit protein levels
- Psmb5 deficiency linked to BRD2; succinylation significantly affected Psmb5 transcription and Trm differentiation
- Heightened BRD2 succinylation attributed to elevated mitochondrial succinyl-CoA in RA T cells
- Targeting succinyl-CoA in CD4+ T cells controlled synovial tissue inflammation in humanized chimeras
Original publication
Mitochondrial Control of Proteasomal Psmb5 Drives the Differentiation of Tissue‐Resident Memory T Cells in Patients with Rheumatoid Arthritis. Arthritis Rheumatol. Published 13 August 2024. doi:10.
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