Selective elimination of pathogenic synovial fluid T-cells from Rheumatoid Arthritis and Juvenile Idiopathic Arthritis by targeted activation of Fas-apoptotic signaling

Bremer, Edwin; Abdulahad, Wayel H.; Bruyn, Marco de; Samplonius, Douwe F.; Kallenberg, Cees G. M.; Armbrust, Wineke; Brouwers, Els; Wajant, Harald; Helfrich, Wijnand

doi:10.1016/j.imlet.2011.04.004

Cited by 15 publications

(7 citation statements)

References 47 publications

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“…We performed RNA-seq of seven CD4 + T cell subsets (naive, Th1, Th17, Th1/17, nonTh1/17, Tfh, and Treg) of peripheral blood taken from RA patients and healthy controls (HC) [ 17 ]). We found that several pathways including GTPase-associated signaling and apoptosis signaling were upregulated in RA as previously reported [ 18 , 19 ]. Weighted gene co-expression network analysis (WGCNA) [ 20 ] identified a gene module that consisted of 227 genes and was correlated with DAS28-CRP.…”

Section: Main Textsupporting

confidence: 87%

Transcriptome analysis of peripheral blood from patients with rheumatoid arthritis: a systematic review

et al. 2018

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In the era of precision medicine, transcriptome analysis of whole gene expression is an essential technology. While DNA microarray has a limited dynamic range and a problem of background hybridization, RNA sequencing (RNA-seq) has a broader dynamic range and a lower background signal that increase the sensitivity and reproducibility. While transcriptome analyses in rheumatoid arthritis (RA) have generally focused on whole peripheral blood mononuclear cells (PBMC), analyses of detailed cell subsets have an increased need for understanding the pathophysiology of disease because the involvement of CD4+ T cells in the pathogenesis of RA has been established. Transcriptome analysis of detailed CD4+ T cell subsets or neutrophils shed new light on the pathophysiology of RA. There are several analyses about the effect of biological treatment. Many studies report the association between type I interferon signature gene expression and response to therapy.

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Section: Main Textsupporting

confidence: 87%

Transcriptome analysis of peripheral blood from patients with rheumatoid arthritis: a systematic review

et al. 2018

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“…Phenotype assessment was determined by immunofluorescent flow cytometric staining essentially as described before [21]. Briefly, distribution of cell populations was analyzed gating on peripheral blood lymphocytes from forward scatter/sideward scatter, detecting CD3 + and CD19 + populations.…”

Section: Methodsmentioning

confidence: 99%

Galectin-9 Activates and Expands Human T-Helper 1 Cells

et al. 2013

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Galectin-9 (Gal-9) is known for induction of apoptosis in IFN-γ and IL-17 producing T-cells and amelioration of autoimmunity in murine models. On the other hand, Gal-9 induced IFN-γ positive T-cells in a sarcoma mouse model and in food allergy, suggesting that Gal-9 can have diametric effects on T-cell immunity. Here, we aimed to delineate the immunomodulatory effect of Gal-9 on human resting and ex vivo activated peripheral blood lymphocytes. Treatment of resting lymphocytes with low concentrations of Gal-9 (5–30 nM) induced apoptosis in ∼60% of T-cells after 1 day, but activated the surviving T-cells. These viable T-cells started to expand after 4 days with up to 6 cell divisions by day 7 and an associated shift from naïve towards central memory and IFN-γ producing phenotype. In the presence of T-cell activation signals (anti-CD3/IL-2) Gal-9 did not induce T-cell expansion, but shifted the CD4/CD8 balance towards a CD4-dominated T-cell response. Thus, Gal-9 activates resting T-cells in the absence of typical T-cell activating signals and promotes their transition to a TH1/C1 phenotype. In the presence of T-cell activating signals T-cell immunity is directed towards a CD4-driven response by Gal-9. Thus, Gal-9 may specifically enhance reactive immunological memory.

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“…In contrast, activated T-cells were sensitive to apoptotic elimination by scFvCD7:FasL, probably due to the intrinsic increase in sensitivity to AICD occurring in T-cells at later activation stages. In actual fact, this T-cell restricted activity profile also enabled the selective elimination of pathogenic synovial fluid T-cells [64]. …”

Section: Fas-ligand (Fasl)mentioning

confidence: 99%

Targeting of the Tumor Necrosis Factor Receptor Superfamily for Cancer Immunotherapy

Bremer

2013

ISRN Oncology

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The tumor necrosis factor (TNF) ligand and cognate TNF receptor superfamilies constitute an important regulatory axis that is pivotal for immune homeostasis and correct execution of immune responses. TNF ligands and receptors are involved in diverse biological processes ranging from the selective induction of cell death in potentially dangerous and superfluous cells to providing costimulatory signals that help mount an effective immune response. This diverse and important regulatory role in immunity has sparked great interest in the development of TNFL/TNFR-targeted cancer immunotherapeutics. In this review, I will discuss the biology of the most prominent proapoptotic and co-stimulatory TNF ligands and review their current status in cancer immunotherapy.

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Selective elimination of pathogenic synovial fluid T-cells from Rheumatoid Arthritis and Juvenile Idiopathic Arthritis by targeted activation of Fas-apoptotic signaling

Cited by 15 publications

References 47 publications

Transcriptome analysis of peripheral blood from patients with rheumatoid arthritis: a systematic review

Transcriptome analysis of peripheral blood from patients with rheumatoid arthritis: a systematic review

Galectin-9 Activates and Expands Human T-Helper 1 Cells

Targeting of the Tumor Necrosis Factor Receptor Superfamily for Cancer Immunotherapy

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