Multiple sclerosis (MS) is an inflammatory demyelinating disease in the central nervous system caused by T cell activation mediated by peripheral macrophages, resulting in severe neurological deficits and disability. Due to the currently limited and expensive treatments for MS, we here introduce an economic Chinese medicine extract, (5R)-5-Hydroxytriptolide (LLDT-8), which shows low toxicity and high immunosuppressive activity. We used the widely accepted mouse model of MS, experimental autoimmune encephalomyelitis (EAE), to examine the immunosuppressive effect of LLDT-8 in vivo. Through the RNA-sequence analysis of peripheral macrophages in EAE mice, we discovered that LLDT-8 alleviates the symptoms of EAE by inhibiting the proinflammatory effect of macrophages, thereby blocking the activation and proliferation of T cells. In all, we found that LLDT-8 could be a potential treatment for MS.
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http://dx.doi.org/10.1016/j.ejphar.2023.176201 | DOI Listing |
Scand J Immunol
January 2025
Department of Neurology, the Second Clinical Medical College, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Fas has been shown to positively regulate the differentiation of T helper 17 (Th17) cells in mouse models of experimental autoimmune encephalomyelitis (EAE). Fas protein expression is regulated by ubiquitination but has not been further studied. In this study, we investigated the role of the Fas ubiquitin ligase in Th17 cell differentiation and highlighted its potential as a therapeutic target for EAE.
View Article and Find Full Text PDFMol Genet Genomics
December 2024
Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Patients with multiple sclerosis (MS) face a heightened risk of developing chronic obstructive pulmonary disease (COPD). Despite this widely reported association, the pathogenic contributors and processes that may favor the development of COPD in MS patients have yet to be identified. Recent studies have suggested peripheral blood leukocytes as a potential link between COPD and autoimmune disorders.
View Article and Find Full Text PDFExp Hematol
December 2024
Division of Experimental Hematology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Experimental Hematology Group, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), Heidelberg, Germany. Electronic address:
Aging exerts a profound impact on the hematopoietic system, leading to increased susceptibility to infections, autoimmune diseases, chronic inflammation, anemia, thrombotic events, and hematologic malignancies. Within the field of experimental hematology, the functional decline of hematopoietic stem cells (HSCs) is often regarded as a primary driver of age-related hematologic conditions. However, aging is clearly a complex multifaceted process involving not only HSCs but also mature blood cells and their interactions with other tissues.
View Article and Find Full Text PDFEBioMedicine
December 2024
Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China. Electronic address:
Background: Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction.
Methods: We employed bioinformatics methodologies to identify human microbial-derived peptides by analyzing their similarity to the MHC II-TCR binding patterns of self-antigens.
Protein Sci
January 2025
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, USA.
G protein Coupled Receptors (GPCRs) are the largest family of cell surface receptors in humans. Somatic mutations in GPCRs are implicated in cancer progression and metastasis, but mechanisms are poorly understood. Emerging evidence implicates perturbation of intra-receptor activation pathway motifs whereby extracellular signals are transmitted intracellularly.
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