Gastrointestinal inflammation prevented by protein sorting factor found in cells lining the gut

October 14, 2011
Figure 1: AP-1B expression in gut epithelial cells prevents bacteria from entering the gut and causing inflammatory bowel diseases. © 2011 Koji Hase

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 inflammation.

IECs are polarized cells, with a bottom surface that attaches to deeper 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 μ1B 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 infiltrated the gut. Mice lacking AP-1B expressed fewer antibacterial proteins, allowing to attack gut (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 μ1B subunit was reduced, and that one cytokine receptor seemed to sort to the wrong portion of the IEC surface. “AP-1B-dependent sorting therefore seems to control epithelial immune functions that keep the human gut healthy,” explains Hase. Enhancing the expression of μ1B could be a potential therapy for Crohn's disease, the team concludes.

Explore further: Researchers find gut bacteria teaches immune cells to see them as friendly

More information: 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). www.gastrojournal.org/article/ … 1%2900611-1/abstract

Related Stories

Researchers find gut bacteria teaches immune cells to see them as friendly

September 22, 2011
(Medical Xpress) -- Most people know that the gut (human or otherwise) has bacteria in it that helps in the proper digestion of food. But how these bacteria manage to evade destruction by the immune system has been a mystery. ...

Transcription factor regulates protein that dampens immune responses

June 17, 2011
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, ...

Bacteria enter via mucus-making gut cells

October 3, 2011
Cells making slippery mucus provide a sticking point for disease-causing bacteria in the gut, according to a study published on October 3 in the Journal of Experimental Medicine.

Recommended for you

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.