Researchers identify key player in the genesis of human intestinal immunity

The trillions of harmful bacteria that populate the human gut represent a continuous threat to our health. Proper intestinal immune function creates a protective barrier between us and the extensive microbial ecosystem in our intestines. Now, researchers at the University of North Carolina School of Medicine have identified the structures that serve as the foundation for the development of the human intestinal immune system.

Specialized immune structures in the intestines, referred to as gut-associated lymphoid tissues, or GALT, are critical components of intestinal immune function. When viruses such as HIV or autoimmune disorders such as inflammatory bowel diseases damage the GALT, intestinal immune function is compromised. The millions of people suffering from such diseases would benefit from therapies that repair damaged GALT. Developing such strategies requires a fundamental understanding of human GALT development.

In mice, specialized aggregates of cells called cryptopatches are the site of GALT development. The presence of similar cell aggregates in human intestines has been controversial. The researchers used humanized mice to demonstrate that cryptopatches serve as the foundation for human GALT formation.

To make this discovery, the researchers bioengineered human immune systems into two very closely related that differed only in their ability to develop cryptopatches. Human GALT structures only developed when cryptopatches were present. In mice where human GALT developed, additional studies revealed that the human GALT facilitated intestinal immune function, including the production of antibodies specifically found in the .

"Our model defines a novel aspect of human GALT development and demonstrates the stepwise process of the intestinal ," said Paul Denton, PhD, research instructor at UNC and an author of the study. "We found evidence that cryptopatches likely work the same way in people and mice."

The study confirms the faithful nature by which the human immune system in these human-mouse chimeric animals recapitulates a normal human immune system.

"This represents a significant advance that will facilitate the study of numerous conditions that affect the gastrointestinal tract," said J. Victor Garcia, PhD, professor of medicine and senior author of the study. "The next step," Garcia said, "is to utilize this model to test regenerative therapies to repair damaged human GALT."

The research was supported by the National Institutes of Health. The article appears in the June 20 issue of the open access journal Cell Reports.

Related Stories

HIV persists in the gut despite long-term HIV therapy

Feb 13, 2008

Even with effective anti-HIV therapies, doctors still have not been able to eradicate the virus from infected individuals who are receiving such treatments, largely because of the persistence of HIV in hideouts known as viral ...

Recommended for you

Study discovers means to free immune system to destroy cancer

Sep 18, 2014

Research led by Paulo Rodriguez, PhD, an assistant research professor of Microbiology, Immunology & Parasitology at LSU Health New Orleans' Stanley S. Scott Cancer Center, has identified the crucial role an inflammatory protein ...

Commensal bacteria help orchestrate immune response in lung

Sep 11, 2014

Studies in mice demonstrate that signals from the bacteria that harmlessly—and often beneficially—inhabit the human gastrointestinal tract boost the immune system's ability to kill a major respiratory pathogen, Klebsiella pn ...

User comments