Sorting out gut health
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).
All news from this category: Life Sciences
Articles and reports from the Life Sciences area deal with applied and basic research into modern biology, chemistry and human medicine.
Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.
Rare quadruple-helix DNA found in living human cells with glowing probes
New probes allow scientists to see four-stranded DNA interacting with molecules inside living human cells, unravelling its role in cellular processes. DNA usually forms the classic double helix shape of…
A rift in the retina may help repair the optic nerve
In experiments in mouse tissues and human cells, Johns Hopkins Medicine researchers say they have found that removing a membrane that lines the back of the eye may improve the…