Notch notches lupus

Tsokos, George C.

doi:10.1016/j.kint.2019.10.018

Cited by 2 publications

(1 citation statement)

References 9 publications

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“…It is widely expressed in many species including vertebrates and invertebrates. It is highly evolutionarily conserved and influences the proliferation and differentiation of almost all cell types ( 27 , 28 ). The classical Notch signaling pathway is mainly composed of Notch, Notch ligand (DSL protein or Jagged1), and CSL (DNA-binding protein).…”

Section: Notch Signaling Pathway Regulates Ra-flsmentioning

confidence: 99%

SFRP1 Negatively Modulates Pyroptosis of Fibroblast‐Like Synoviocytes in Rheumatoid Arthritis: A Review

et al. 2022

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Secreted frizzled-related protein 1 (SFRP1) is a member of secretory glycoprotein SFRP family. As a primitive gene regulating cell growth, development and transformation, SFRP1 is widely expressed in human cells, including various cancer cells and fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA). Deletion or silencing of SFRP1 involves epigenetic and other mechanisms, and participates in biological behaviors such as cell proliferation, migration and cell pyroptosis, which leads to disease progression and poor prognosis. In this review, we discuss the role of SFRP1 in the pathogenesis of RA-FLS and summarize different experimental platforms and recent research results. These are helpful for understanding the biological characteristics of SFRP1 in RA, especially the mechanism by which SFRP1 regulates RA-FLS pyroptosis through Wnt/β-catenin and Notch signaling pathways. In addition, the epigenetic regulation of SFRP1 in RA-FLS is emphasized, which may be considered as a promising biomarker and therapeutic target of RA.

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Section: Notch Signaling Pathway Regulates Ra-flsmentioning

confidence: 99%

SFRP1 Negatively Modulates Pyroptosis of Fibroblast‐Like Synoviocytes in Rheumatoid Arthritis: A Review

et al. 2022

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Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus

Yuan,

Liu,

Zhang

et al. 2024

Rheumatology

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Objectives Patients with systemic lupus erythematosus (SLE) display heightened immune activation and elevated IgG autoantibody levels, indicating compromised regulatory T cell (Tregs) function. Our recent findings pinpoint CD8+ Tregs as crucial regulators within secondary lymphoid organs, operating in a NOX2-dependent mechanism. However, the specific involvement of CD8+ Tregs in SLE pathogenesis and the mechanisms underlying their role remain uncertain. Methods SLE and healthy individuals were enlisted to assess the quantity and efficacy of Tregs. CD8+CD45RA+CCR7+ Tregs were generated ex vivo, and their suppressive capability was gauged by measuring pZAP70 levels in targeted T cells. Notch1 activity was evaluated by examining activated Notch1 and HES1, with manipulation of Notch1 accomplished with Notch inhibitor DAPT, Notch1 shRNA, and Notch1-ICD. To create humanized SLE chimeras, immune-deficient NSG mice were engrafted with PBMCs from SLE patients. Results We observed a reduced frequency and impaired functionality of CD8+ Tregs in SLE patients. There was a downregulation of NOX2 in CD8+ Tregs from SLE patients, leading to a dysfunction. Mechanistically, the reduction of NOX2 in SLE CD8+ Tregs occurred at a post-translational level rather than at the transcriptional level. SLE CD8+ Tregs exhibited heightened Notch1 activity, resulting in increased expression of STUB1, an E3 ubiquitin ligase that binds to NOX2 and facilitates its ubiquitination. Consequently, restoring NOX2 levels and inhibiting Notch1 activity could alleviate the severity of the disease in humanized SLE chimeras. Conclusion Notch1 is the cell-intrinsic mechanism underlying NOX2 deficiency and CD8+ Treg dysfunction, serving as a therapeutic target for clinical management of SLE.

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Notch notches lupus

Cited by 2 publications

References 9 publications

SFRP1 Negatively Modulates Pyroptosis of Fibroblast‐Like Synoviocytes in Rheumatoid Arthritis: A Review

SFRP1 Negatively Modulates Pyroptosis of Fibroblast‐Like Synoviocytes in Rheumatoid Arthritis: A Review

Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus

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