Immune system compensates for 'leaky gut' in inflammatory bowel disease susceptibility
September 13, 2012 in Immunology
New research could clarify how inflammatory bowel diseases (IBD), conditions that include ulcerative colitis and Crohn's disease, are triggered and develop.
Scientists at Emory University School of Medicine have shown how the immune system can compensate for a "leaky gut" and prevent disease in mice that are susceptible to intestinal inflammation. These findings could explain why some individuals who are susceptible to developing IBD do or do not get the disease.
The results will be published online Sept. 13 in the journal Immunity.
"Our results suggest that when there is a chronically leaky intestine, defects in the immune system need to be present for the development of IBD," says senior author Charles Parkos, MD, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine.
"Breakdown of the intestinal barrier can occur as a result of intestinal infections or stress. The normal response involves several components of the immune system that help to heal the injury while controlling invading bacteria. When this normal response is defective and there is a leaky barrier, the risk of developing IBD is increased."
Parkos and co-senior author Tim Denning, PhD, assistant professor of pediatrics, and their colleagues have been studying mice that are deficient in a protein called JAM-A (junctional adhesion molecule A). JAM-A is an important regulator of the epithelial barrier in the intestine. Denning describes JAM-A and other "tight junction" molecules as forming a seal between epithelial cells like a zipper, which keeps bacteria away from the rest of the body.
JAM-A deficient mice have a "leaky gut," meaning that chemicals and bacteria can cross more easily from the insides of the intestines to the rest of the body. Passage of bacteria across the intestinal wall and into the body can cause inflammation and disease. JAM-A deficient mice have more bacteria in the liver and lymph nodes, and they are more susceptible than regular mice to a chemical treatment (DSS) that induces colitis (intestinal inflammation). Surprisingly, despite these defects, JAM-A deficient mice do not develop spontaneous colitis.
"This is a situation that may be analogous to first degree relatives of people with Crohn's disease," Parkos says. "Some of these people have increased intestinal permeability, which suggests that they are more susceptible to developing disease, but they don't get sick. Gut permeability also transiently increases in normal people based on what we eat and drink, yet disease doesn't occur. We think that immune compensation is what protects the body under these conditions."
The researchers wanted to dissect which types of immune cells were responsible for this compensatory effect. To this end, they treated JAM-A deficient mice with antibodies that depleted certain types of immune cells or, in some cases, examined mice with additional genetic changes in combination with the JAM-A deficiency. They found that a type of immune cell, CD4+ T cells, is needed to produce signals that encourage production of a type of antibody, IgA. IgA is especially important for limiting incursions by bacteria in the intestine.
"In normal mice, immune cells such as CD4+ T cells and IgA-producing B cells do not play a big role in DSS-triggered colitis," Denning says. "But if the mice have a preexisting leak, the immune system plays an important role."
Under normal conditions, B cells are needed to produce IgA, which helps to keep bacteria from invading through the intestinal wall. While defects in the production of IgA alone do not result in colitis, the presence of a chronically leaky gut in concert with IgA deficiency results in increased susceptibility to abnormal intestinal inflammation that involves other types of immune cells. During intestinal inflammation, the amount of JAM-A in the epithelium can decrease, thus further weakening the intestinal barrier.
"There is a 'chicken or the egg' question with respect to whether inflammation or alterations in the intestinal barrier come first," Parkos says. "Many people with IBD report that their first severe episode was brought on by a stressful event or an intestinal illness, and it is possible that these events serve as a trigger that starts a vicious cycle of altered barrier and inflammation."
More information: M. Khounlotham et al. Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis. Immunity 31, 1-11 (2012).
Journal reference:
Immunity
Provided by
Emory University
-
Il-22 gene delivers the goods and decreases intestinal inflammation
Jan 02, 2008 |
not rated yet |
0
-
Novel cytokine protects mice from colitis
Aug 23, 2011 |
not rated yet |
0
-
Friend or Foe? Scientists Determine How the Intestine Keeps Us Safe From Microbial Invaders
Feb 21, 2007 |
not rated yet |
0
-
First step to new therapy for chronic bowel disease
Jul 06, 2010 |
not rated yet |
0
-
Bacteria identified that may lead to inflammatory bowel disease in certain individuals
Sep 16, 2010 |
not rated yet |
0
-
Motion perception revisited: High Phi effect challenges established motion perception assumptions
Apr 23, 2013 |
3 / 5 (2) |
2
-
Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update)
Apr 02, 2013 |
4.5 / 5 (11) |
5
-
The visual system as economist: Neural resource allocation in visual adaptation
Mar 30, 2013 |
5 / 5 (2) |
9
-
Separate lives: Neuronal and organismal lifespans decoupled
Mar 27, 2013 |
4.9 / 5 (8) |
0
-
Sizing things up: The evolutionary neurobiology of scale invariance
Feb 28, 2013 |
4.8 / 5 (10) |
14
-
The Durability of Bone: Long Falls
6 hours ago
-
Is energy convertible to matter?
8 hours ago
-
Rotating electron as a dipole is this right?
10 hours ago
-
Dipole term in multipole expansion
14 hours ago
-
Bubbles in a Pre-Boiling/Boiling pot of water
15 hours ago
-
Assumptions of Griffith's fracture theory
May 21, 2013
- More from Physics Forums - Classical Physics
More news stories
New immune system discovered
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
Immunology
May 20, 2013 |
4.8 / 5 (22) |
8
|
Vitamin D could provide new and effective treatments for asthma
(Medical Xpress)—Scientists at King's College London have discovered that Vitamin D has the potential to significantly reduce the symptoms of asthma. The study, led by Professor Catherine Hawrylowicz from ...
Immunology
May 20, 2013 |
5 / 5 (1) |
0
|
Immune protein could stop diabetes in its tracks
Melbourne researchers have identified an immune protein that has the potential to stop or reverse the development of type 1 diabetes in its early stages, before insulin-producing cells have been destroyed.
Immunology
May 20, 2013 |
5 / 5 (5) |
0
|
Stem-cell-based strategy boosts immune system in mice
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology
May 16, 2013 |
4.8 / 5 (5) |
0
|
Resistance to visceral leishmaniasis: New mechanisms involved
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology
May 16, 2013 |
not rated yet |
0
Phthalates: Study links chemicals widely found in plastics, processed food to elevated blood pressure in children, teens
Plastic additives known as phthalates (pronounced THAL-ates) are odorless, colorless and just about everywhere: They turn up in flooring, plastic cups, beach balls, plastic wrap, intravenous tubing and—according to the ...
If you can remember it, you can remember it wrong
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
B vitamins could delay dementia
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
Insight into the dazzling impact of insulin in cells
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
New sleeping pill poised to hit US markets
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
Reducing caloric intake delays nerve cell loss
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...