Regulatory T cells (Tregs) are a subpopulation of lymphocytes that play a role in suppressing and regulating immune responses. Recently, it was suggested that controlling the functions and activities of Tregs might be applicable to the treatment of human diseases such as autoimmune diseases, organ transplant rejection, and graft-versus-host disease. TNF receptor type 2 (TNFR2) is a target molecule that modulates Treg functions. In this study, we investigated the role of TNFR2 signaling in the differentiation and activation of mouse Tregs. We previously reported the generation of a TNFR2-selective agonist TNF mutant, termed R2agoTNF, by using our unique cytokine modification method based on phage display. R2agoTNF activates cell signaling via mouse TNFR2. In this study, we evaluated the efficacy of R2agoTNF for the proliferation and activation of Tregs in mice. R2agoTNF expanded and activated mouse CD4CD25 Tregs ex vivo. The structural optimization of R2agoTNF by internal cross-linking or IgG-Fc fusion selectively and effectively enhanced Treg expansion in vivo. Furthermore, the IgG-Fc fusion protein suppressed skin-contact hypersensitivity reactions in mice. TNFR2 agonists are expected to be new Treg expanders.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4049/jimmunol.2000871 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
COP II-mediated ER-to-Golgi transport is a bottleneck for IgNAR-Fc production in the Chinese hamster ovary cell expression system.
J Biosci Bioeng
February 2025
Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address:
The novel heavy-chain antibody known as immunoglobulin new antigen receptor (IgNAR) is derived from cartilaginous fishes such as sharks. IgNAR, which binds to antigens with the high specificity and affinity of a conventional IgG antibody and exhibits high resistance to denaturation, has potential as a next-generation antibody in biopharmaceutical and biotechnological applications. High-level expression of recombinant IgNAR in animal cells has been challenging.
View Article and Find Full Text PDFA first-in-human, randomized study of the safety, pharmacokinetics and pharmacodynamics of povetacicept, an enhanced dual BAFF/APRIL antagonist, in healthy adults.
Clin Transl Sci
November 2024
Alpine Immune Sciences, a Vertex Company, Seattle, Washington, USA.
Therapeutic agents targeting the tumor necrosis factor (TNF) superfamily cytokines B-cell activating factor (BAFF, BLyS) and/or A PRoliferation Inducing Ligand (APRIL) have demonstrated clinical effectiveness in multiple autoimmune diseases, such as systemic lupus erythematosus, lupus nephritis, and immunoglobulin A nephropathy (IgAN). However, their clinical utility can often be limited by incomplete and/or prolonged times to clinical response and inconvenient dosing regimens, which may be improved by more potent dual inhibition of both cytokines. Povetacicept (ALPN-303; TACI vTD-Fc) is a crystallizable fragment (Fc) fusion protein of an engineered transmembrane activator and CAML interactor (TACI) domain which mediates more potent inhibitory activity than wild-type TACI-Fc or BAFF- or APRIL-specific antibodies and demonstrates superior pharmacokinetic and pharmacodynamic activity in multiple preclinical disease models.
View Article and Find Full Text PDFAltered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children.
Open Forum Infect Dis
November 2024
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Background: Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines.
View Article and Find Full Text PDFRhesus Macaque Killer Cell Ig-like Receptor Domain 0 Glycans Impact Surface Expression and Ligand Specificity.
J Immunol
December 2024
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI.
Article Synopsis
- The study focuses on understanding how glycosylation affects the function of killer cell Ig-like receptors (KIRs) in rhesus macaques, which are important for natural killer (NK) cell biology and immunogenetics.
- Researchers identified that certain KIRs have a unique three-amino acid deletion that influences their glycosylation patterns, resulting in different ligand recognition capabilities.
- Through experiments involving mutations to N-glycan sites, the study demonstrates that glycosylation impacts both the surface expression of KIRs and their ability to bind to MHC class I ligands, with specific implications for receptor functionality.
Single domain antibody-scFv conjugate targeting amyloid β and TfR penetrates the blood-brain barrier and interacts with amyloid β.
MAbs
October 2024
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Article Synopsis
- Neurodegenerative diseases like Alzheimer's are challenging for patients and healthcare systems, especially in aging populations, with immunotherapies like lecanemab and donanemab facing issues due to limited delivery across the blood-brain barrier (BBB).
- A study evaluated camelid single-domain antibodies (VHHs) combined with human antibodies to improve brain delivery, showing that specific fusion proteins could achieve significant brain concentrations and highlighted the importance of optimal binding to the transferrin receptor (TfR).
- Results from experiments in mouse models demonstrated that these VHH-based fusion proteins could effectively target the brain, potentially overcoming BBB limitations for better therapeutic and diagnostic applications in Alzheimer's disease.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!