Related Experiment Video

Updated: Oct 2, 2025

Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
10:10

Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity

Published on: November 8, 2016

8.9K

Local inhibition of TGF-β1 signaling improves Th17/Treg balance but not joint pathology during experimental arthritis

Joyce Aarts1, Arjan van Caam1, Xinlai Chen1

  • 1Department of Experimental Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center (Radboudumc), PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

Scientific Reports
|February 25, 2022
PubMed

TGF-β1 is an important growth factor to promote the differentiation of T helper 17 (Th17) and regulatory T cells (Treg). The potential of TGF-β1 as therapeutic target in T cell-mediated diseases like rheumatoid arthritis (RA) is unclear. We investigated the effect of TGF-β1 inhibition on murine Th17 differentiation in vitro, on human RA synovial explants ex vivo, and on the development of experimental arthritis in vivo. Murine splenocytes were differentiated into Th17 cells, and the effect of the TGF-βRI inhibitor SB-505124 was studied. Synovial biopsies were cultured in the presence or absence of SB-505124. Experimental arthritis was induced in C57Bl6 mice and treated daily with SB-505124. Flow cytometry analysis was performed to measure different T cell subsets. Histological sections were analysed to determine joint inflammation and destruction. SB-505124 potently reduced murine Th17 differentiation by decreasing Il17a and Rorc gene expression and IL-17 protein production. SB-505124 significantly suppressed IL-6 production by synovial explants. In vivo, SB-505124 reduced Th17 numbers, while increased numbers of Tregs were observed. Despite this skewed Th17/Treg balance, SB-505124 treatment did not result in suppression of joint inflammation and destruction. Blocking TGF-β1 signalling suppresses Th17 differentiation and improves the Th17/Treg balance. However, local SB-505124 treatment does not suppress experimental arthritis.

More Related Videos

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes12:59

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes

Published on: September 26, 2013

34.8K
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice07:37

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice

Published on: June 6, 2025

424

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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...
1.5K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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...
7.9K
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
10.3K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.5K
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

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...
282
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

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...
249