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Autoimmune Disorders: Molecular Mechanisms and Therapeutic Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 700

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Guest Editor
Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Warsaw Medical University, 02-097 Warsaw, Poland
Interests: rheumatoid arthritis; pathophysiology; biological therapies; systemic connective tissue diseases; scleroderma; interstitial lung disease
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Special Issue Information

Dear Colleagues,

Autoimmune disorders encompass a broad spectrum of diseases driven by dysregulated immune responses that lead to chronic inflammation, autoantibody production, and progressive tissue damage. Understanding the molecular mechanisms underlying these conditions is crucial for developing targeted therapies that can modulate the immune response while minimizing adverse effects.

This Special Issue, “Autoimmune Disorders: Molecular Mechanisms and Therapeutic Strategies”, aims to provide a comprehensive insight into the pathophysiology of autoimmune diseases.

This Special Issue explores the molecular mechanisms driving autoimmunity, including genetic predisposition, epigenetic modifications, and dysregulated immune signaling. Aberrant activation of T and B cells, defective regulatory T cells, and abnormal cytokine profiles contribute to chronic inflammation and tissue damage.

Advancements in molecular research have identified key signaling pathways involved in autoimmune pathogenesis, such as NF-κB, JAK-STAT, and PI3K-AKT-mTOR. Understanding these pathways has facilitated the development of targeted therapies, including monoclonal antibodies, small-molecule inhibitors, and immune checkpoint modulators. Biologics such as TNF-α inhibitors, IL-6 antagonists, and CD20-targeting therapies have revolutionized treatment approaches, improving disease outcomes in conditions like rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis.

Emerging therapeutic strategies focus on restoring immune tolerance through regulatory T cell expansion, tolerogenic dendritic cells, and antigen-specific immunotherapy. Advances in precision medicine and biomarker discovery are enhancing personalized treatment, optimizing drug responses, and minimizing adverse effects. This Special Issue highlights current molecular insights and therapeutic innovations in autoimmune diseases, emphasizing translational research that bridges basic immunology with clinical applications.

Dr. Katarzyna Romanowska-Próchnicka
Guest Editor

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Keywords

  • molecular mechanisms
  • immune signaling pathways
  • targeted therapies
  • biomarkers
  • autoimmune pathogenesis

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Published Papers (1 paper)

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Research

17 pages, 6136 KB  
Article
Emodin Attenuates Rheumatoid Arthritis by Modulating the NF-κB/HIF-1α/VEGF Signaling Pathway
by Dehao Du, Yihang Lou, Linlan Zhou, Jiayu Tian, Tingdan Zhang, Zexuan Qiu and Xiaofeng Rong
Int. J. Mol. Sci. 2026, 27(8), 3460; https://doi.org/10.3390/ijms27083460 - 12 Apr 2026
Viewed by 222
Abstract
This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) [...] Read more.
This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling axis. Bovine type II collagen-induced arthritis (CIA) mouse models and lipopolysaccharide (LPS)-stimulated EA.hy926 endothelial cells were utilized in this study. The effects of EMO on joint pathological alterations, the expression of NF-κB/HIF-1α/VEGF axis proteins, inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)), and angiogenic capacity were assessed using histopathological analysis, Western blotting, immunohistochemistry (IHC), immunofluorescence, and tube formation assays. Furthermore, small interfering RNA (siRNA) interference targeting key molecules was employed to validate the molecular mechanisms underlying the therapeutic effects of EMO. In the CIA model group, the ankle joints of mice exhibited pronounced inflammatory infiltration, synovial hyperplasia, and bone destruction. Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-κB pathway proteins, HIF-1α, and VEGF in joint tissues (p < 0.001). In vitro experiments revealed that EMO treatment significantly reduced the LPS-induced secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) (p < 0.001), and decreased both the number and total length of tubular structures formed by endothelial cells compared to the control (p < 0.001). Notably, siRNA-mediated knockdown of p65 resulted in decreased intracellular protein levels of HIF-1α and VEGF, accompanied by a significant reduction in tube formation (p < 0.001). This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-κB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1α/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA. Full article
(This article belongs to the Special Issue Autoimmune Disorders: Molecular Mechanisms and Therapeutic Strategies)
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