Interleukin-10 (IL-10) is an anti-inflammatory cytokine protein that reduces immune responses and staves off autoimmune disease. Now, a research team led by Masato Kubo at the RIKEN Research Center for Allergy and Immunology, Yokohama, has identified a transcription factor called E4 promoter-binding protein (E4BP4) that is responsible for driving the expression of IL-10 in multiple types of immune cells.
Figure 1: In T cells stained blue (top left), the transcription factor E4BP4 (red) regulates that production of IL-13 (green) and IL-10 (not shown)
Copyright : Yasutaka Motomura et al.
The researchers investigated E4BP4 because of a unique property of a subset of immune cells called T helper type 1 (TH1) cells, which generally enhance immune responses by secreting pro-inflammatory cytokines. However, under chronic stimulation with foreign antigens—that occur during chronic infection—TH1 cells can also produce cytokines, such as IL-10 and IL-13, which are normally made only by other immune-cell types. While the immune system is fighting the infection, IL-13 modulates allergic responses, and IL-10 prevents the immune system from attacking the body.
Kubo and colleagues compared genes expressed in TH1 cells with and without chronic antigen stimulation, and found that E4BP4 was expressed only in instances of chronic antigen stimulation. When they expressed E4BP4 in TH1 cells that had not been chronically infected, it induced production of IL-10 and IL-13 in conditions in which those cytokines would not normally occur (Fig. 1). E4BP4-deficient TH1 cells could not increase expression of IL-10 and IL-13 after chronic antigen stimulation. The researchers found that other T cell subsets also required E4BP4 to modulate the expression of IL-10, but not IL-13.
Transcription factors can control the expression of genes by binding to a region on the genomic DNA called the promoter. Kubo and colleagues observed that E4BP4 bound to the IL-13 promoter in TH1 cells that had been chronically stimulated with antigen. No binding occurred with TH1 cells lacking chronic stimulation. Kubo explains, however, that: “E4BP4 seems to regulate the expression of IL-10 in a totally different way—by altering the chromosomal structure in the region of that gene.”
Mice lacking IL-10 can spontaneously develop intestinal autoimmune disease. Interestingly, Kubo and his team found that E4BP4-deficient mice produced lower levels of IL-10 than control mice, and showed some symptoms of gastrointestinal inflammation along with diarrhea. The mice lacking E4BP4 also developed more severe symptoms of a neurological autoimmune disease caused by exposure to brain antigens. E4BP4 is therefore a key factor in preventing the immune system from attacking the body’s own organs, and “induction of expression of E4BP4 may cure many types of autoimmune inflammatory diseases,” says Kubo.
The corresponding author for this highlight is based at the Open Laboratory for Allergy Research, RIKEN Research Center for Allergy and Immunology
 Motomura, Y., Kitamura, H., Hijikata, A., Matsunaga, Y., Matsumoto, K., Inoue, H., Atarashi, K., Hori, S., Watarai, J., Zhu, J., Taniguchi, M. & Kubo, M. The transcription factor E4BP4 regulations the production of IL-10 and IL-13 in CD4+ T cells. Nature Immunology 12, 450–459 (2011).
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences