Vasculitogenic T Cells in Large Vessel Vasculitis

Watanabe, Ryu; Hashimoto, Motomu

doi:10.3389/fimmu.2022.923582

Cited by 15 publications

(9 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, low-dose IL-2 therapy has been expected to be effective against autoimmune diseases such as SLE because it can expand CD4 + Tregs [ 33 , 43 ]. The anti-IL-6 inhibitor tocilizumab can also restore the number and functions of CD4 + Tregs [ 17 , 44 , 45 ]; however, these effects on CD8 + Tregs are unknown [ 46 ]. Several attempts to expand CD8 + Tregs using probiotics or by in vitro or in vivo procedures are under investigation to treat autoimmunity [ 20 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

CD8+ Regulatory T Cell Deficiency in Elderly-Onset Rheumatoid Arthritis

Watanabe¹,

Kadoba

Tamamoto³

et al. 2023

JCM

Self Cite

View full text Add to dashboard Cite

Elderly-onset rheumatoid arthritis (EORA) is associated with higher disease activity and accelerated joint destruction compared with young-onset RA (YORA). However, the underlying immunological mechanism remains unclear. Regulatory T cells (Tregs) are an immunosuppressive T cell subset, and CD4+ Tregs are deficient and/or dysfunctional in RA; however, CD8+ Tregs have not been fully examined in RA. Here, we aimed to determine the role of CD8+ Tregs, particularly in EORA. A total of 40 patients (EORA, n = 17; YORA, n = 23) were cross-sectionally enrolled. Current disease activity and treatment were comparable between the two groups; however, levels of multiple cytokines, including IL-1β, TNFα, interferon (IFN)-γ, IL-2, and IL-10, were significantly increased in EORA. The number of CD4+ Tregs did not differ between the groups (p = 0.37), but those of CD8+ Tregs were significantly decreased in EORA (p = 0.0033). The number of CD8+ Tregs were inversely correlated with plasma matrix metalloprotease (MMP)-3 levels (r = −0.3331, p = 0.036). Our study results revealed an intrinsic deficiency of CD8+ Tregs in patients with EORA, which leaves synovitis unchecked with excessive MMP-3 release. A therapeutic approach to restore CD8+ Tregs may provide a new avenue for the treatment of EORA.

show abstract

Section: Discussionmentioning

confidence: 99%

CD8+ Regulatory T Cell Deficiency in Elderly-Onset Rheumatoid Arthritis

Watanabe¹,

Kadoba

Tamamoto³

et al. 2023

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…CD4+ and CD8+ T cells play central roles in the pathogenesis of LVV ( 75 , 76 ). Recent evidence suggests that Th1- and CD8-mediated inflammation may be less responsive to TCZ treatment, whereas the molecular signatures of Th17, Tfh, and Treg cells are improved.…”

Section: Discussionmentioning

confidence: 99%

Changes in the molecular profiles of large-vessel vasculitis treated with biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors

et al. 2023

View full text Add to dashboard Cite

Giant cell arteritis and Takayasu arteritis are two types of primary large-vessel vasculitis (LVV). Although glucocorticoids (GC) are the standard treatment for LVV, the disease relapse rates are high. Recent clinical trials on biological disease-modifying anti-rheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors have demonstrated their efficacy in reducing LVV relapse rates and GC dosages. However, the control of residual inflammation and degenerative alterations in the vessel wall remains an outstanding requirement in the clinical management of LVV. The analysis of immune cell phenotypes in patients with LVV may predict their response to treatment with bDMARDs and JAK inhibitors and guide their optimal use. In this mini-review, we focused on molecular markers, including the immune cell proportions and gene expression, in patients with LVV and in mouse models of LVV treated with bDMARDs and JAK inhibitors.

show abstract

“…PTRRC can play a pro-apoptotic and anti-apoptotic role by activating Akt through PI3K, and the activation of Akt signaling can inhibit a variety of pro-apoptotic factors. The rapamycin complex (mTOR) is located downstream of Akt, especially mTORC1 (part of mTOR) regulates the differentiation and function of effector T cells by integrating microenvironmental factors [21] . It has been reported that in GCA, mTORC1 is continuously active and provides energy for the development of GCA by synthesizing ATP through the glycolytic pathway [22] .…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic screening of genes associated with giant cell arteritis and therapeutic agents

Yao

Zhang

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective To analyze the high-throughput sequencing data of giant cell arteritis by bioinformatics technology, to initially identify the core genes associated with giant cell arteritis and to explore potential therapeutic agents. Methods Gene expression profile (GSE174694) was obtained from the Gene Expression Database (GEO), and the differential genes were calculated, the differentially expressed genes were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG), and the protein interaction network was constructed to obtain the core genes. Finally, drug correlation analysis (connectivity map, CMap) was used to identify small molecule drugs with potential therapeutic effects on giant cell arteritis. Results A total of 771 differentially expressed genes were screened, including 481 up-regulated and 290 down-regulated. The GO analysis showed that the differentially expressed genes were mainly involved in cell surface receptor signaling pathway, T cell receptor signaling pathway, cell adhesion and intrinsic immune response, and the KEGG pathway analysis showed that the differentially expressed genes were mainly involved in chemokine signaling pathway, Th17 cell differentiation and Th1 and Th2 cell differentiation. The KEGG pathway analysis showed that the differential genes were mainly involved in chemokine signaling pathway, Th17 cell differentiation and Th1 and Th2 cell differentiation. The protein interaction network was constructed to screen five core genes, PTPRC, FCGR2B, ITGAM, SPI1 and ITGB2, which were mainly involved in promoting T cell value-added and differentiation, inhibiting apoptosis, increasing cell adhesion and promoting inflammatory response. CMap analysis suggested that small molecules such as warfarin A and anisomycin have potential therapeutic effects on giant cell arteritis. The CMap analysis suggested the potential therapeutic effects of small molecules such as warfarin A and anisomycin on giant cell arteritis. Conclusion This study provides a holistic view of the gene transcriptome in giant cell arteritis, and the core genes and small molecule drugs screened may provide new ideas for the pathogenesis of giant cells and drug development.

show abstract

Vasculitogenic T Cells in Large Vessel Vasculitis

Cited by 15 publications

References 108 publications

CD8+ Regulatory T Cell Deficiency in Elderly-Onset Rheumatoid Arthritis

CD8+ Regulatory T Cell Deficiency in Elderly-Onset Rheumatoid Arthritis

Changes in the molecular profiles of large-vessel vasculitis treated with biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors

Bioinformatic screening of genes associated with giant cell arteritis and therapeutic agents

Contact Info

Product

Resources

About