Researchers identify key player in the genesis of human intestinal immunity

June 20, 2013

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.

Explore further: Good bugs gone bad: Gut immune cells keep beneficial microbes in their place

Related Stories

Recommended for you

Epigenomic changes are key to innate immunological memory

August 31, 2015

A research team led by Keisuke Yoshida and Shunsuke Ishii of the RIKEN Molecular Genetics Laboratory has revealed that epigenomic changes induced by pathogen infections, mediated by a transcription factor called ATF7, are ...

Team finds early inflammatory response paralyzes T cells

August 18, 2015

In a discovery that is likely to rewrite immunology text books, researchers at UC Davis have found that early exposure to inflammatory cytokines, such as interleukin 2, can "paralyze" CD4 T cells, immune components that help ...

SIV shrugs off antibodies in vaccinated monkeys

August 11, 2015

New research on monkeys vaccinated against HIV's relative SIV calls into question an idea that has driven AIDS vaccine work for years. The assumption: a protective vaccine only needs to stimulate moderate levels of antibodies ...

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.