The gastrointestinal tract is lined with intestinal epithelial cells (IECs) that maintain gut health by keeping bacteria and pro-inflammatory immune cells from infiltrating gut tissues.
Now, a team of researchers in Japan has shown that a protein in these cells, which is responsible for sorting many proteins to particular portions of the IEC surface, plays a key role in IEC modulation of gut inflammation1.
IECs are polarized cells, with a bottom surface that attaches to deeper gut tissues, and a top surface that faces the inside of the gut, where it is exposed to ingested food and gut-resident bacteria. Proteins that are created in the cell are sorted preferentially to either the top or the bottom portion of the IEC. For example, cytokine receptors are shuttled mainly to the bottom of IECs so they can respond to cytokines released by immune cells within deeper gut tissues. Led by Koji Hase at the RIKEN Research Center for Allergy and Immunology in Yokohama, the researchers thought that disruption of proper protein sorting could affect the ability of IECs to properly respond to their environment.
To test their theory, the researchers generated mice lacking the ì1B subunit for a sorting protein called adaptor protein-1B (AP-1B). These mice developed an inflammatory gut disease called colitis, in which large number of immune cells infiltrated the gut. Mice lacking AP-1B expressed fewer antibacterial proteins, allowing bacteria to attack gut tissue (Fig. 1). Hase and colleagues showed that this bacterial entry enhanced immune cell recruitment into the gut, because antibiotics could reduce the inflammation in these mice.
Cytokines such as interleukin-17 (IL-17) are responsible for inducing antibacterial protein expression in IECs. However, the researchers found that cells lacking AP-IB were unable to properly sort cytokine receptors, including the IL-17 receptor, to the appropriate portion of the IEC membrane. This suggested that IECs may have failed to properly respond to IL-17 because its receptors were in the wrong part of the cell.
When Hase and colleagues examined IECs in humans with an inflammatory bowel condition called Crohn’s disease, they found that expression of the ì1B subunit was reduced, and that one cytokine receptor seemed to sort to the wrong portion of the IEC surface. “AP-1B-dependent protein sorting therefore seems to control epithelial immune functions that keep the human gut healthy,” explains Hase. Enhancing the expression of ì1B could be a potential therapy for Crohn's disease, the team concludes.
The corresponding author for this highlight is based at the Laboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology.
Takahashi, D., Hase, K., Kimura, S., Nakatsu, F., Ohmae, M., Mandai, Y., Sato, T., Date, Y., Ebisawa, M., Kato, T., et al. The epithelia-specific membrane trafficking factor AP-1B controls gut immune homeostasis in mice. Gastroenterology 141, 621–632 (2011).
gro-pr | Research asia research news
Family of crop viruses revealed at high resolution for the first time
15.10.2019 | John Innes Centre
Receptor complexes on the assembly line
15.10.2019 | Albert-Ludwigs-Universität Freiburg im Breisgau
Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.
The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...
Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.
Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...
A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.
The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...
Superconductivity has fascinated scientists for many years since it offers the potential to revolutionize current technologies. Materials only become superconductors - meaning that electrons can travel in them with no resistance - at very low temperatures. These days, this unique zero resistance superconductivity is commonly found in a number of technologies, such as magnetic resonance imaging (MRI).
Future technologies, however, will harness the total synchrony of electronic behavior in superconductors - a property called the phase. There is currently a...
How do some neutron stars become the strongest magnets in the Universe? A German-British team of astrophysicists has found a possible answer to the question of how these so-called magnetars form. Researchers from Heidelberg, Garching, and Oxford used large computer simulations to demonstrate how the merger of two stars creates strong magnetic fields. If such stars explode in supernovae, magnetars could result.
How Do the Strongest Magnets in the Universe Form?
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
15.10.2019 | Materials Sciences
15.10.2019 | Interdisciplinary Research
15.10.2019 | Life Sciences