Related Experiment Video
Updated: Sep 16, 2025
07:09
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
7.6K
Molecular Signatures of Dendritic Cell Activation upon TNF Stimulation: A Multi-Omics Study in Rheumatoid Arthritis
Alina Alshevskaya1, Shakir Suleimanov1, Elizaveta Sheveleva1
1Laboratory of Immune Engineering, Federal State Autonomous Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119048 Moscow, Russia.
International Journal of Molecular Sciences
|July 12, 2025
Summary
Dendritic cells (DCs) in rheumatoid arthritis (RA) show increased inflammation markers and a heightened response to tumor necrosis factor alpha (TNF). RA-derived DCs exhibit unique TNF-driven gene expression changes, unlike those from healthy individuals.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Dendritic cells (DCs) are key players in rheumatoid arthritis (RA) pathogenesis.
- The role of tumor necrosis factor alpha (TNF) in regulating DCs in RA is not fully understood.
Purpose of the Study:
- To investigate the impact of TNF on dendritic cells in RA patients using single-cell multi-omics.
- To characterize the phenotypic and transcriptional changes in DCs from RA patients upon TNF stimulation.
Main Methods:
- Utilized CITE-seq (single-cell multi-omics) to analyze peripheral blood mononuclear cells (PBMCs) from RA patients and healthy donors.
- Integrated surface protein and transcriptomic data to identify changes in dendritic cell populations.
- Applied in vitro TNF stimulation to assess DC responsiveness.
Main Results:
- Dendritic cells from RA patients displayed an inflammatory phenotype with elevated CD14 and CD16 expression.
- RA-derived DCs showed significant upregulation of genes related to antigen presentation, migration, and inflammation after TNF stimulation.
- Healthy control DCs did not exhibit similar activation patterns upon TNF stimulation.
Conclusions:
- Dendritic cells in RA patients possess a TNF-responsive, pro-inflammatory transcriptional program.
- TNF receptor signaling critically influences DC function in the context of RA.
- Dendritic cells represent a potential therapeutic target for personalized immunomodulatory treatments in RA.
Related Concept Videos
01:24T Cell Types and Functions
1.4K
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...
1.4K
01:20The JAK-STAT Signaling Pathway
9.3K
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...
9.3K
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
237
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...
237
02:26NF-κB-dependent Signaling Pathway
7.9K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.9K
01:22T Cell Activation and Clonal Selection
5.2K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
5.2K