Immune mediated inflammatory diseases: moving from targeted biologic therapy, stem cell therapy to targeted cell therapy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 7, 2025

Despite the advancements in targeted biologic therapy for immune-mediated inflammatory diseases (IMIDs), significant challenges persist, including drug maintenance, primary and secondary non-responses, adverse effects. Recent data have strengthened evidence supporting stem cell as an experimental salvage into a standard treatment option. preclinical clinical studies suggested that chimeric antigen receptor T (CAR-T) therapy, which depleting tissue bone marrow B cells, may lead to improvement, even inducing long-lasting remissions patients with IMIDs. In this review, we address unmet needs of delineate critical differences between transplantation CAR-T evaluate current status IMIDs explore its potential existing limitations.

Language: Английский

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Pathophysiology in Systemic Sclerosis: Current Insights and Future Perspectives

Sclerosis, Journal Year: 2025, Volume and Issue: 3(2), P. 17 - 17

Published: May 27, 2025

Background: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vasculopathy, autoimmunity, and fibrosis. Due to its low prevalence heterogeneous clinical presentation, early diagnosis remains challenging, often delaying appropriate treatment. The progresses from microvascular dysfunction, manifesting as Raynaud’s phenomenon, systemic fibrosis affecting multiple organs, including the lungs, gastrointestinal tract, heart, kidneys. There have been considerable advancements in understanding pathophysiology of during last few years this has already resulted improvement therapeutic approaches used control organ-specific manifestations. However, underlying cause still incompletely elucidated. Methods: Here, we summarize current knowledge on SSc pathogenesis. Results: involves an interplay chronic inflammation, impaired vascular function, excessive extracellular matrix deposition, leading progressive organ damage. Endothelial dysfunction driven immune-mediated injury, oxidative stress, imbalance vasoconstrictors vasodilators, capillary loss hypoxia. Autoantibodies against endothelial cells or other toxic factors induce apoptosis impair angiogenesis, further exacerbating Despite increased angiogenic factor levels, repair mechanisms are defective, resulting ischemic Dysregulated immune responses involving Th2 cytokines, B cells, macrophages contribute fibroblast activation collagen deposition. Transforming growth factor-beta (TGF-β) plays central role fibrotic progression, while fibroblasts resist apoptosis, perpetuating scarring. abnormally stiff, reinforcing creating self-perpetuating cycle. Conclusions: Advances molecular cellular facilitated targeted therapies, yet effective disease-modifying treatments remain limited. Future research should focus precision medicine approaches, integrating biomarkers novel therapeutics improve patient outcomes.

Language: Английский

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Activation of eIF2α-ATF4 by endoplasmic reticulum-mitochondria coupling stress enhances COX2 expression and MSC-based therapeutic efficacy for rheumatoid arthritis

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 28, 2025

Mesenchymal stem/stromal cell (MSC) therapy holds promise as a therapeutic strategy for rheumatoid arthritis (RA). However, the loss of secretory function following delivery has significantly restricted its clinical application. Our preliminary studies confirmed that endoplasmic reticulum stress (ERS)-MSCs greatly inhibited RA follicular helper T cells (Tfh) through cyclooxygenase-2 (COX2)/prostaglandin E2 (PGE2) pathway activation via an unknown molecular mechanism, demonstrating effects ERS-modified MSCs on RA. To compare their efficacy, thapsigargin (TG)-stimulated or unstimulated were transplanted into collagen-induced (CIA) mice. Joint inflammation was evaluated from both general and histological aspects. Splenocytes isolated, flow cytometry performed to assess proportions 1 (Th1), Th17, Tfh subsets. Additionally, levels TNF-α in mouse serum measured using ELISA. For mechanistic exploration, TRRUST Cistrome Data Browser databases used analyse transcription factors related COX2 regulation, well target genes regulated by activating factor 4 (ATF4). identify most effective treatment concentration duration inducing ERS, we conducted time gradient analysis TG qRT‒PCR CCK‒8 assay. Then, western blotting employed determine level ATF4 ERS-MSCs. verify vivo, ATF4-overexpressing CIA mice, joint Th1, Th17 subsets analysed. clarify regulatory mechanism leading activation, protein kinase RNAs, such (PERK)/phosphorylated-PERK (p-PERK) eukaryotic initiation 2α (eIF2α)/phosphorylated-eIF2α (p-eIF2α) examined. Furthermore, eIF2α/p-eIF2α assessed after PERK blockade. Mitochondrial subsequently examined Finally, when blocking ERS mitochondrial separately simultaneously, reevaluated. Compared with MSCs, ERS-MSCs exhibited greater efficacy Public bioinformatics analyses role COX2, experimental methods further demonstrated ATF4-transfected alleviated We also during induction, PERK-mediated eIF2α phosphorylation contributes ATF4. provoked ERS-MSCs, synergistically unmodified enhanced immunosuppressive potency, primarily overexpression, which activation. Moreover, jointly expression. This study reveals novel enhancing properties thereby presents promising MSC-based

Language: Английский

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Allogeneic CD19-targeted CAR-T therapy in refractory systemic lupus erythematosus achieved durable remission

Med, Journal Year: 2025, Volume and Issue: unknown, P. 100749 - 100749

Published: May 1, 2025

Language: Английский

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