Related Experiment Video
Updated: Oct 6, 2025
07:46
Author Spotlight: Achieving High-Purity In Vitro Differentiation of Th17 Cells Using Cytokine Concentration Modulation
Published on: October 25, 2024
3.5K
Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation
Reiko Matsumoto1, Teruki Dainichi1, Soken Tsuchiya2
1Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
JCI Insight
|August 10, 2018
Summary
Epithelial cells
Area of Science:
- Immunology
- Dermatology
- Cellular Biology
Background:
- Epithelial cells are crucial for immune defense and adaptive immunity, including T helper 17 (Th17) responses.
- The specific epithelial signaling pathways essential for robust IL-17-mediated immunity remain largely undefined.
- Understanding these pathways is key to addressing IL-17-driven inflammatory conditions.
Purpose of the Study:
- To investigate the role of specific epithelial signaling pathways in IL-17-mediated immune responses.
- To determine if keratinocyte Tumor Necrosis Factor Receptor Associated Factor 6 (TRAF6) is essential for psoriatic inflammation.
- To elucidate the contribution of epithelial TRAF6 to the development of IL-17-driven inflammation.
Main Methods:
- Utilized a mouse model of imiquimod-induced psoriatic inflammation.
- Generated conditional knockout mice with TRAF6 specifically deleted in keratinocytes.
- Assessed dendritic cell activation, cytokine production (IL-23), and T cell responses (IL-17, γδ T cells).
- Evaluated other immune responses like contact hypersensitivity and IgE production to assess TRAF6 specificity.
Main Results:
- Keratinocyte-specific deletion of TRAF6 abrogated imiquimod-induced psoriatic inflammation in mice.
- Loss of TRAF6 in keratinocytes impaired dendritic cell activation, IL-23 production, and IL-17 production by γδ T cells.
- TRAF6 deficiency did not affect other immune responses, indicating a specific role in IL-17-mediated inflammation.
- Administration of IL-23 restored IL-17 production but not psoriatic pathology, highlighting TRAF6's role beyond IL-23 sensing.
Conclusions:
- Epithelial TRAF6 signaling is indispensable for the full development of IL-17-mediated psoriatic inflammation.
- TRAF6 in keratinocytes plays a critical role in both initiating and sustaining psoriatic inflammation.
- Targeting epithelial TRAF6 signaling may offer a therapeutic strategy for IL-17-driven skin diseases like psoriasis.
Related Concept Videos
01:24T Cell Types and Functions
1.5K
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...
1.5K
01:16TGF - β Signaling Pathway
7.9K
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
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.3K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.3K