Interferon‐γ facilitated adjuvant‐induced arthritis at early stage

Ma, Hua; Xu, Minwen; Zhang, Ting; Yin, Hanqiu; Yin, Shi

doi:10.1111/sji.12757

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…To improve our work in the future, it is necessary to evaluate mouse models that can better mimic the microenvironment of rheumatoid arthritis, and furthermore, in consideration of clinical translation, a humanized mouse model warrants evaluation. The optical dye IRDye680 we employed belongs to NIR-I (700–900 nm), with the advantage of non-radioactive, convenient, easy preparation, and low cost NIR-I imaging is suitable for superficial disease imaging, such as RA, systemic lupus erythematosus (SLE), and melanoma [ 25 ]. But due to its poor penetration, NIR-I imaging often fails in deep tissue imaging, which limits further translation.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Imaging OX40+ Activated T Cells Provides Early Warning of Rheumatoid Arthritis

Lei

et al. 2023

Mol Imaging Biol

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Purpose The goal of this study was to develop an imaging probe—IRDye-680RD-OX40 mAb—that can be used for noninvasive imaging and optical imaging of rheumatoid arthritis (RA). OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T cell activation. Detectable change in T cell activation profiles was observed in early RA. Methods OX40 expression pattern was analyzed by flow cytometry. N-hydroxysuccinimide (NHS) esters are used to label proteins selectively on free amino groups of OX40 monoclonal antibody (mAb). Characterization of IRDye-680RD-OX40 mAb was measured and a fluorescence spectrum gathered. Cell binding assay was also performed between activated and naïve murine T cells. Longitudinal near-infrared fluorescence (NIRF) imaging of the probe was performed on day 8, day 9, day 10, and day 11 of adjuvant-induced arthritis (AIA) mouse model. Paw thickness and body weight were compared between the OX40 mAb and IgG injection groups. Results NIRF imaging with IRDye-680RD-OX40 mAb revealed strong OX40-positive responses with high specificity. Flow analysis showed that OX40 was specifically expressed on the surface of T cells in RP and spleen of AIA model. The AIA group was significantly differentiated from the control group at all time points with imaging monitoring. The region of interest (ROI) was in line with ex vivo imaging and biodistribution study. This study highlights the potential utility of the OX40 NIRF imaging as a new strategy for RA prediction and T cell monitoring. Conclusion The results provide evidence that IRDye-680RD-OX40 mAb detects organized T cells activation in early RA. The optical probe was capable of detection of RA pathogenesis. It identified transcriptional responses to RA that mediate its immune functions. Thus, it may be an ideal probe for RA imaging. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Noninvasive Imaging OX40+ Activated T Cells Provides Early Warning of Rheumatoid Arthritis

Lei

et al. 2023

Mol Imaging Biol

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“…As emphasized in one recent work devoted to this topic, in this model, IFN-γ may play a key role in the extension of arthritis at the early stage. This cytokine produced by T-helper cells, CD4+, was involved in the induction of pro-inflammatory cytokines (TNF and Il-1β) and reprogramming the vascular network, which resulted in changes in vascular permeability, thus permitting autoantibodies to enter the target tissues [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Short Peptides of Innate Immunity Protein Tag7 Inhibit the Production of Cytokines in CFA-Induced Arthritis

Telegin

Chernov

Minakov

et al. 2022

IJMS

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The pathogenesis of autoimmune arthritis is a hot topic in current research. The main focus of this work was to study cytokines released in CFA-induced arthritis in ICR mice as well as the regulation of blood levels of cytokines by two peptides of the innate immunity protein Tag7 (PGLYRP1) capable of blocking the activation of the TNFR1 receptor. Arthritis was induced by local periarticular single-dose injections of 40 µL of complete Freund’s adjuvant (CFA) into the left ankle joints of mice. The levels of chemokines and cytokines in plasma were measured using a Bio-Plex Pro Mouse Cytokine Kit at 3, 10, and 21 days after arthritis induction. Tag7 peptides were shown to decrease the blood levels of the pro-inflammatory cytokines IL-6, TNF, and IL-1β. Administration of peptides also decreased the levels of chemokines MGSA/CXCL1, MIP-2α/CXCL2, ENA78/CXCL5, MIG/CXCL9, IP-10/CXCL10, MCP-1/CCL2, and RANTES/CCL5. Furthermore, a decrease in the levels of cytokines IL7, G-CSF, and M-CSF was demonstrated. Addition of the studied peptides strongly affected IFN-γ concentration. We believe that a decrease in the levels of cytokine IFN-γ was associated with a therapeutic effect of Tag7 peptides manifested in alleviation of the destruction of cartilage and bone tissues in the CFA-induced arthritis.

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“…Especially TNF-α, which is also produced by synovial macrophages, B-, and NK-cells is one of the most important mediators of joint inflammation in RA [60]. It is present in most arthritic biopsies and its overexpression induces spontaneous inflammation in various rodent arthritis models [61]. Early in vitro studies demonstrated that TNF-α could induce both cartilage degradation [62] and bone resorption [63].…”

Section: Contribution Of Cytokines To Inflammation In Ramentioning

confidence: 99%

Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

Lin

Anzaghe

Schülke

2020

Cells

530

376

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Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.

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Interferon‐γ facilitated adjuvant‐induced arthritis at early stage

Cited by 5 publications

References 32 publications

Noninvasive Imaging OX40+ Activated T Cells Provides Early Warning of Rheumatoid Arthritis

Noninvasive Imaging OX40+ Activated T Cells Provides Early Warning of Rheumatoid Arthritis

Short Peptides of Innate Immunity Protein Tag7 Inhibit the Production of Cytokines in CFA-Induced Arthritis

Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

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