Unraveling the Immunometabolism Puzzle: Deciphering Systemic Sclerosis Pathogenesis DOI Creative Commons
Maryam Masoumi,

Ali Bodaghi,

Hossein Khorramdelazad

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(15), P. e35445 - e35445

Published: July 31, 2024

The article delves into the pathogenesis of systemic sclerosis (SSc) with an emphasis on immunometabolism dysfunctions. SSc is a complex autoimmune connective tissue disorder skin and organ fibrosis manifestation, vasculopathy, immune dysregulation. A growing amount research indicates that plays significant role in diseases, including SSc. review explores intricate interplay between dysfunction metabolic alterations, focusing metabolism glucose, lipids, amino acids, TCA (tricarboxylic acid) cycle, oxidative stress disease. According to recent research, there are changes various pathways could trigger or perpetuate Glycolysis play pivotal through inducing fibrosis. Dysregulated fatty acid β-oxidation (FAO) consequent lipid result dysregulated extracellular matrix (ECM) breakdown induction. altered acids can significantly be involved mechanisms. Reactive oxygen species (ROS) production has crucial damage patients. Indeed, involvement highlighted, which offers potential therapeutic avenues. underscores need for comprehensive studies unravel multifaceted mechanisms driving progression.

Language: Английский

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee DOI Creative Commons
Raffaella Greco, Tobias Alexander, Nicoletta Del Papa

et al.

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 69, P. 102476 - 102476

Published: Feb. 10, 2024

Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T (CART) regulatory (Tregs), have been successfully adopted in ADs. An international expert panel the European Society for Blood Marrow Transplantation International Cell Gene Therapy, reviewed all available evidence, based on current literature practices, use MSC, CART Tregs, AD patients rheumatological, neurological, gastroenterological indications. Expert-based consensus recommendations best practice quality patient care were developed to support clinicians, scientists, their multidisciplinary teams, as well providers will be regularly updated.

Language: Английский

Citations

31
Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers DOI Open Access

Nicole Chizara Oparaugo,

Kelsey Ouyang,

Nam Phuong N. Nguyen

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1527 - 1527

Published: Jan. 12, 2023

Regulatory T cells (Tregs) play an important role in maintaining immune tolerance and homeostasis by modulating how the system is activated. Several studies have documented critical of Tregs suppressing functions effector antigen-presenting cells. Under certain conditions, can lose their suppressive capability, leading to a compromised system. For example, mutations Treg transcription factor, Forkhead box P3 (FOXP3), drive development autoimmune diseases multiple organs within body. Furthermore, reduction numbers or change function facilitate autoimmunity, whereas overabundance inhibit anti-tumor anti-pathogen immunity. This review discusses characteristics mechanism action select skin diseases, transplantation, cancer. We also examine potential Tregs-based cellular therapies autoimmunity.

Language: Английский

Citations

28
Novel therapeutic strategies for autoimmune and inflammatory rheumatic diseases DOI Creative Commons
Renaud Felten, Philippe Mertz, E. Sebbag

et al.

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(7), P. 103612 - 103612

Published: May 8, 2023

Drugs of unknown mechanisms action are no longer being developed because we have largely capitalized on our improved understanding the immunopathogenesis immune-mediated inflammatory diseases (IMIDs) to develop therapeutic monoclonal antibodies (mAbs) and targeted treatments. These therapies profoundly revolutionized care IMIDs. However, heterogeneity IMIDs redundancy molecular pathways, some patients with might not respond a specific drug or their disease relapse secondarily. Therefore, there is much at stake in development new strategies, which include combinations mAbs bispecific (BsMAbs), nanobodies nanoparticles (NPs), vaccines, small interfering RNA (siRNA) interference, autologous hematopoietic stem cell transplantation (aHSCT), chimeric antigen receptor (CAR)-T cells. With broad pipeline treatments clinical development, paradigm rapidly evolving from whether drugs will be available complex selection most adequate treatment (or combination) patient level. This change highlights need better characterize heterogeneous immunological spectrum these diseases. Only then novel strategies able fully demonstrate potential treat

Language: Английский

Citations

14
An international perspective on the future of systemic sclerosis research DOI
David Abraham,

Carol M. Black,

Christopher P. Denton

et al.

Nature Reviews Rheumatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Language: Английский

Citations

0
New and future therapies: Changes in the therapeutic armamentarium for SLE DOI
Anca Askanase, Leila Khalili, Wei Tang

et al.

Best Practice & Research Clinical Rheumatology, Journal Year: 2023, Volume and Issue: 37(4), P. 101865 - 101865

Published: Aug. 24, 2023

Language: Английский

Citations

9
Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders DOI Creative Commons
Michael L. Samulevich, Liam E. Carman, Brian J. Aneskievich

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2723 - 2723

Published: Nov. 28, 2024

Successful skin wound healing is dependent on an interplay between epidermal keratinocytes and dermal fibroblasts as they react to local extracellular factors (DAMPs, PAMPs, cytokines, etc.) surveyed from that environment by numerous membrane receptors (e.g., TLRs, cytokine receptors, etc.). In turn, those are the start of a cytoplasmic signaling pathway where balance key effective and, needed, cell matrix regeneration. When directed through NF-κB, these routes lead transient responses benefit initiating immune recruitment, replication, chemokine production, protein synthesis. The converse can also occur, ongoing canonical NF-κB activation leads chronic, hyper-responsive states. Here, we assess three players, TAK1, TNFAIP3, TNIP1, in regulation activation, which, because their distinctive yet inter-related functions, either promote or limit activation. Their balanced function integral successful healing, given significant control over expression inflammation-, fibrosis-, remodeling-associated genes. Intriguingly, proteins have been emphasized dysregulated central systemic sclerosis (SSc). Notably, diffuse SSc shares some tissue features similar excessive inflammatory/fibrotic response without eventual resolution. Taking cue certain instances aberrant having shared aspects, e.g., chronic inflammation fibrosis, this review looks for first time, our knowledge, at what pathologies might common regarding progression NF-κB-mediated signaling. Additionally, while TNIP1 often investigated reported individually, propose them here whose consequences very highly interconnected focus NF-κB. We thus highlight emerging promise clinical derived improved understanding signal modulators. Depending protein, its indirect direct pharmacological has reported. Current findings support further intensive studies points both basic healthy cells well with goal targeting translational multiple cutaneous situations, whether stemming acute injury response.

Language: Английский

Citations

2
Innovative cell therapies for systemic sclerosis: available evidence and new perspectives DOI

Alain Lescoat,

Monalisa Ghosh, Stephan Kadauke

et al.

Expert Review of Clinical Immunology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 15

Published: Sept. 16, 2024

Systemic sclerosis (SSc) is the rheumatic disease with highest individual mortality rate a detrimental impact on quality of life. Cell-based therapies may offer new perspectives for this as recent phase I trials support safety IV infusion allogeneic mesenchymal stromal cells in SSc and case reports highlight potential use Chimeric Antigen Receptor (CAR)-T targeting CD19 active patients who have not responded to conventional immunosuppressive therapies.

Language: Английский

Citations

1
CART Cells and Other Cell Therapies (ie MSC, Tregs) in Autoimmune Diseases DOI Creative Commons
Raffaella Greco, Dominique Farge

Springer eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 837 - 848

Published: Jan. 1, 2024

Language: Английский

Citations

0
MiR-4769-3p suppresses adipogenesis in systemic sclerosis by negatively regulating the USP18/VDAC2 pathway DOI Creative Commons

Bingsi Tang,

Jiangfan Yu, Rui Tang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(8), P. 110483 - 110483

Published: July 11, 2024

Language: Английский

Citations

0
Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents DOI Creative Commons
Nicoletta Del Papa,

Silvia Cavalli,

Andrea Rindone

et al.

Arthritis Research & Therapy, Journal Year: 2024, Volume and Issue: 26(1)

Published: Oct. 23, 2024

Abstract Background Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there still a paucity data comparing AHSCT rituximab (RTX). Aim study to retrospectively compare, dcSSc, effectiveness that RTX and CIT. Methods Thirty-five dcSSc AHSCT-treated were compared 29 36 matched cases treated CIT, respectively. The followed up for 5 years by assessing selected measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC DLCO), revised EUSTAR Activity Index (REAI) chosen evaluate therapy efficacy. Results was significantly CIT prolonging inducing rapid reduction mRSS REAI maintaining baseline level longer time. also superior reducing REAI, saving function. Conclusion both survival prolonged remission dcSSc.

Language: Английский

Citations

0