Vaccines prevent reinduction of rheumatoid arthritis symptoms in collagen-induced arthritis mouse model

Thumsi, Abhirami; Swaminathan, Srivatsan J; Mangal, Joslyn L.; Suresh, Abhirami P.; Acharya, Abhinav P.

doi:10.1007/s13346-023-01333-8

Cited by 8 publications

(1 citation statement)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A scoring strategy shown in Figure 3a was employed [15,16]. It was observed that by day 32, there was a significantly lower level of Arthritis score in PPP-bc2 treated mice as compared to PPP and no treatment mice in right rear paw (Figure 3b).…”

Section: Ppp Releasing Bovine Collagen Type II (Bc2) With a Decreasin...mentioning

confidence: 99%

Exponentially decreasing exposure of antigen generates anti-inflammatory T-cell responses

Esrafili,

Kupfer,

Thumsi

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Rheumatoid Arthritis (RA) is a chronic debilitating disease characterized by auto-immune reaction towards self-antigen such as collagen type II. In this study, we investigated the impact of exponentially decreasing levels of antigen exposure on pro-inflammatory T-cell responses in the collagen-induced arthritis (CIA) mouse model. Using a controlled delivery experimental approach, we manipulated the collagen type II (CII) antigen concentration presented to the immune system. We observed that exponentially decreasing levels of antigen generated reduced pro-inflammatory T-cell responses in secondary lymphoid organs in mice suffering from RA. Specifically, untreated mice exhibited robust pro-inflammatory T cell activation and increased paw inflammation, whereas, mice exposed to exponentially decreasing concentrations of CII demonstrated significantly reduced pro-inflammatory T cell responses, exhibited lower levels of paw inflammation, and decreased arthritis scores in the right rear paw. The data also demonstrate that the decreasing antigen levels promoted the induction of regulatory T cells (Tregs), which play a crucial role in maintaining immune tolerance and suppressing excessive inflammatory responses. Our findings highlight the importance of antigen concentration in modulating pro-inflammatory T cell responses in the CIA model. These results provide valuable insights into the potential therapeutic strategies that target antigen presentation to regulate immune responses and mitigate inflammation in rheumatoid arthritis and other autoimmune diseases. Further investigations are warranted to elucidate the specific mechanisms underlying the antigen concentration-dependent modulation of T-cell responses and to explore the translational potential of this approach for the development of novel therapeutic interventions in autoimmune disorders.

show abstract

Section: Ppp Releasing Bovine Collagen Type II (Bc2) With a Decreasin...mentioning

confidence: 99%

Exponentially decreasing exposure of antigen generates anti-inflammatory T-cell responses

Esrafili,

Kupfer,

Thumsi

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Engineered Tumor–Immune Microenvironment On A Chip to Study T Cell–Macrophage Interaction in Breast Cancer Progression

Manoharan,

Ravi,

Suresh

et al. 2024

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

Evolving knowledge about the Tumor Immune Microenvironment (TIME) is driving innovation in designing novel therapies against hard‐to‐treat breast cancer. Targeting the immune components of TIME has emerged as a promising approach for cancer therapy. While recent immunotherapies aim at restoring antitumor immunity, counteracting tumor escape remains challenging. Hence there is a pressing need to better understand the complex tumor‐immune crosstalk within TIME. Considering this imperative, this study aimed at investigating the crosstalk between the two abundant immune cell populations within the breast TIME – macrophages and T cells, in driving tumor progression using an organotypic 3D in vitro tumor on‐a‐chip (TOC) model. The TOC featured distinct yet interconnected organotypic tumor and stromal entities. Our tri‐culture platform mimicked the complex TIME, embedding the two immune populations in a suitable 3D matrix. Analysis of invasion, morphometric measurements, and flow cytometry results underscores the substantial contribution of macrophages to tumor progression, while the presence of T cells was associated with a deceleration in the migratory behavior of both cancer cells and macrophages. Furthermore, cytokine analyses revealed significant upregulation of Leptin and RANTES in triculture. Overall, this study highlights the complexity of TIME and the critical role of immune cells in cancer progression.This article is protected by copyright. All rights reserved

show abstract

Inverse‐Vaccines for Rheumatoid Arthritis Re‐establish Metabolic and Immunological Homeostasis in Joint Tissues

Thumsi,

Martínez,

Swaminathan

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) causes inflammatory and metabolic imbalances in tissue, which then exacerbates inflammation in affected joints. Therefore, restoring tissue homeostasis is necessary for the remission of RA symptoms. In fact, the changes in immunological and metabolic tissue homeostasis at different stages of the disease is not well understood. Herein, the changes in the immunological metabolic profiles in different stages of RA namely, early, intermediate, and late stage was examined. Moreover, the efficacy of the microparticle inverse‐vaccine, paKG(PFK15+bc2) to restore immunological and metabolic tissue homeostasis at different stages of the disease was also investigated. Analysis of the immune cell profiles revealed that there was a significant decrease in the activation of pro‐inflammatory immune cells while a remarkable increase was seen in regulatory T‐cell populations in the intermediate and late stages of RA in the inverse‐vaccine treated group as compared to no treatment. Also, it was determined that glycolysis in the spleen was normalized in the late stages of CIA, which was similar to no disease tissues. Using metabolomics we identified, key metabolites UDP‐glucuronic acid and L‐Glutathione oxidized that were significantly altered between treatment groups, and thus might provide new druggable targets for RA. We also employed flux metabolic modeling of the metabolomics data to identify amino acid and carnitine pathways as the central pathways affected at the tissue‐level in CIA as the disease progresses. Overall, this study shows that the inverse‐vaccines initiate early re‐establishment of homeostasis and persists through the disease span.This article is protected by copyright. All rights reserved

show abstract

Vaccines prevent reinduction of rheumatoid arthritis symptoms in collagen-induced arthritis mouse model

Cited by 8 publications

References 66 publications

Exponentially decreasing exposure of antigen generates anti-inflammatory T-cell responses

Exponentially decreasing exposure of antigen generates anti-inflammatory T-cell responses

Engineered Tumor–Immune Microenvironment On A Chip to Study T Cell–Macrophage Interaction in Breast Cancer Progression

Inverse‐Vaccines for Rheumatoid Arthritis Re‐establish Metabolic and Immunological Homeostasis in Joint Tissues

Contact Info

Product

Resources

About