Related Experiment Video
Updated: Aug 28, 2025
09:51
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
10.8K
Synthetic TGF-β Signaling Agonist-Treated Dendritic Cells Induce Tolerogenicity and Antirheumatic Effects
Ji-Soo Oh1, Sung-Uk Hwang1,2, Kyung-Eun Noh1
1Department of Biotechnology, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam 13488, Korea.
Current Issues in Molecular Biology
|September 22, 2022
Summary
The novel compound T74, a TGF-β signaling agonist, was used to treat dendritic cells (DCs). T74-treated DCs reduced arthritis symptoms and increased regulatory T cells in a mouse model, indicating an antirheumatic effect.
Area of Science:
- Immunology
- Rheumatology
- Pharmacology
Background:
- Tolerogenic dendritic cells (tDCs) exhibit immunosuppressive properties beneficial for autoimmune diseases.
- Transforming growth factor-beta (TGF-β) signaling is crucial in immune regulation.
- The small molecule TGF-β signaling agonist T74 is a novel compound targeting this pathway.
Purpose of the Study:
- To evaluate the antirheumatic potential of T74-treated dendritic cells (T74-DCs) in a collagen-induced arthritis (CIA) mouse model.
- To investigate the immunomodulatory effects of T74 on dendritic cell function.
- To assess the impact of T74-DCs on T cell differentiation and regulatory T cell (Treg) induction.
Main Methods:
- Bone marrow-derived dendritic cells (DCs) from DBA/1J mice were treated with LPS, type II collagen, and T74 to generate T74-DCs.
- T74-DCs and untreated DCs (NT-DCs) were characterized for surface molecule and cytokine expression.
- In vitro assays assessed the differentiation of effector T cells and regulatory T cells (Tregs).
- Collagen-induced arthritis (CIA) was established in DBA/1J mice, followed by treatment with T74-DCs or NT-DCs.
Main Results:
- T74-DCs displayed reduced expression of molecules associated with antigen presentation and T cell stimulation.
- T74-DCs showed diminished capacity to differentiate effector T cells but enhanced Treg differentiation in vitro.
- Mice treated with T74-DCs exhibited ameliorated joint inflammation in the CIA model.
- T74-DC treatment led to increased Treg populations in vivo compared to control groups.
Conclusions:
- The compound T74 induces a tolerogenic phenotype in dendritic cells.
- T74-modified DCs exert significant antirheumatic effects in a CIA mouse model.
- T74-mediated DC therapy holds promise for treating autoimmune arthritis through Treg induction.
Related Concept Videos
01:24T Cell Types and Functions
1.3K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.3K
01:16TGF - β Signaling Pathway
7.6K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.6K
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
215
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
215
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
256
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
256