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The type III histone deacetylase silent information regulator 1 (SIRT1) is an enzyme that is critical for the modulation of immune and inflammatory responses. However, the data on its role in rheumatoid arthritis (RA) are limited and controversial. To better understand how SIRT1 regulates adaptive immune responses in RA, we evaluated collagen-induced arthritis (CIA) in myeloid cell-specific SIRT1 knockout (mSIRT1 KO) and wild-type (WT) mice. Arthritis severity was gauged on the basis of clinical, radiographic and pathologic scores. Compared with their WT counterparts, the mSIRT1 KO mice exhibited less severe arthritis, which was less destructive to the joints. The expression levels of inflammatory cytokines, matrix metalloproteinases and ROR-γT were also reduced in the mSIRT1 KO mice compared with the WT mice and were paralleled by reductions in the numbers of Th1 and Th17 cells and CD80- or CD86-positive dendritic cells (DCs). In addition, impaired DC maturation and decreases in the Th1/Th17 immune response were observed in the mSIRT1 KO mice. T-cell proliferation was also investigated in co-cultures with antigen-pulsed DCs. In the co-cultures, the DCs from the mSIRT1 KO mice showed decreases in T-cell proliferation and the Th1/Th17 immune response. In this study, myeloid cell-specific deletion of SIRT1 appeared to suppress CIA by modulating DC maturation. Thus, a careful investigation of DC-specific SIRT1 downregulation is needed to gauge the therapeutic utility of agents targeting SIRT1 in RA.
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AMPK suppresses Th2 cell responses by repressing mTORC2
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Defect of SIRT1-FoxO3a axis is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated cellular senescence and nematode aging
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SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity
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Chronic LCMV infection regulates the effector T cell response by inducing the generation of less immunogenic dendritic cells
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SIRT5-related desuccinylation modification of AIFM1 protects against compression-induced intervertebral disc degeneration by regulating mitochondrial homeostasis
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Deacetylation of CHK2 by SIRT1 protects cells from oxidative stress-dependent DNA damage response
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KSY-PH1 Prevents UVB-Induced Damage and Promotes Wound Healing In Skin Cells via Coregulation of Sirt1 and Pin1
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