Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Blood levels of the extracellular matrix protein nephronectin (Npnt), a protein critical for kidney development, are elevated in autoimmune experimental autoimmune encephalitis (EAE) mice, which are a model for multiple sclerosis. We found here that treatment with anti-Npnt antibody directed against the αβ integrin-binding site (Npnt-blocking antibody) inhibits EAE development. The selenium transporter selenoprotein P (SeP) was identified as a novel Npnt-binding partner. In EAE, Npnt induced SeP and glutathione peroxidase 1 (GPx1) expression, followed by reactive oxygen species (ROS) inhibition in CD4 T cells; these changes were disturbed by Npnt-blocking antibody treatment, which also caused suppressed differentiation of interleukin (IL)-17-producing CD4 T-helper cells (Th17s) and elevated differentiation of regulatory T cells (Tregs). Treatment of EAE mice with the ROS scavenger -acetyl cysteine (NAC) blocked the Npnt-blocking antibody-induced decrease in Th17 differentiation and increase in Treg differentiation. In conclusion, the interaction between Npnt and SeP contributes to EAE development by regulating the Th17/Treg balance via the ROS level.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1152/ajpcell.00376.2021 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Type I interferon limits central nervous system autoimmunity by modulating the microRNA-21-FOXO1 axis in pathogenic T helper 17 cells.
Sci Transl Med
September 2025
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
IFN-β, a type I interferon, has been used as a first-line therapy for patients with multiple sclerosis (MS) for more than 30 years; however, the cellular and molecular basis of its therapeutic efficacy remains unclear. Here, we first used experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, to show that the therapeutic effects of IFN-β were associated with a down-regulation of microRNA-21 (miR-21) and pathogenic T17 (pT17) cells. In vitro experiments demonstrated that genetic knockout of miR-21 directly inhibited pathogenic T17 cell differentiation.
View Article and Find Full Text PDFImportance of responder criteria for reporting health-related quality-of-life data in clinical trials for advanced cancer: recommendations of Common Sense Oncology and the European Organisation for Research and Treatment of Cancer.
Lancet Oncol
September 2025
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands.
The goals of treatment for people with advanced cancer are to prolong survival and improve symptoms and health-related quality of life (HRQOL). Although many phase 3 randomised clinical trials seek to evaluate HRQOL during treatment, informing individual patients about expected HRQOL outcomes is challenging, as the common method of analysis and reporting compares averages for randomised groups, and clinicians find these data difficult to apply in clinical practice. Symptomatic patients with advanced cancer would like to know the probability that a proposed treatment might improve their survival or their dominant symptoms, and the probability of having treatment-related side-effects.
View Article and Find Full Text PDFThe thyroid hormone receptor beta (TR-β) signaling controls pathogenic Th17 cells in autoimmune disease.
Int Immunol
August 2025
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
The role of the thyroid hormone receptor beta (TR-β) in the immune system remains poorly understood; although its effect on TGF-βsignaling has been reported in non-immune systems. Here, we report that Thrb is highly expressed in pathogenic CD4+ T cells that infiltrate the central nervous system during experimental autoimmune encephalomyelitis (EAE) and Thrb is exclusively expressed in IL-17-producing CD4+ T cells (Th17 cells) that develop both in vitro or in vivo. Sobetirome, a selective TR-βagonist, promoted pathogenic Th17 differentiation and IL-17 production in the presence of exogenous IL-1β.
View Article and Find Full Text PDFFollicular regulatory T cells promote experimental autoimmune encephalomyelitis by supporting B cell egress from germinal centers.
Sci Transl Med
August 2025
Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France.
Follicular regulatory T cells (T cells) constitute a subset of regulatory T cells pivotal to the immune response in germinal centers (GCs) that inhibit autoantibody production. Their role, however, remains ill-defined in autoimmune diseases like multiple sclerosis (MS) and its murine model, experimental autoimmune encephalomyelitis (EAE), which are neuroinflammatory diseases driven by T and B cells. Here, we quantified peripheral blood immune subpopulations in two cohorts of patients with MS and found higher circulating T cell frequencies in patients in relapse compared with patients in remission.
View Article and Find Full Text PDFTargeting Talin1 to reprogram dendritic cell activation landscapes: A mechanistically grounded cell therapy for multiple sclerosis model.
Neurotherapeutics
August 2025
Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China; Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China. Electronic address:
This study investigated the role of Talin1 in regulating dendritic cell (DC) activation and the neuroprotective benefits of Talin1-knockdown DCs in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Bone marrow-derived DCs (BMDCs) were transduced with shTalin1 lentiviral vectors in vitro. Their morphological and biochemical profiles, surface molecules expression, cytokines production, capacity to induce T cell responses, as well as regulatory mechanisms, were comprehensively assessed.
View Article and Find Full Text PDF