Gut patrolling: a fascinating new perspective on driving T cells to protect the gut

Gut cells send secret messages to the immune system. Thanks to new research from the La Jolla Institute for Immunology (LJI), scientists finally know what they’re talking about.

Scientific Immunology

reveals how barrier cells lining the gut send messages to patrolling T cells that reside there. These cells communicate by expressing a protein called HVEM, which prompts T cells to live longer and move more to thwart potential infections.

“This study shows how barrier cells, structural elements of tissue and resident immune cells in the gut communicate to provide host defense,” said Mitchell Kronenberg, Ph.D., senior author of the new study and LJI professor and chief scientific officer.

Barrier cells called epithelia form a single-cell-thick layer that lines the gut like a busy Queue like a row. nightclub. Epithelial cells huddle together, jostling and chatting with each other. Meanwhile, T-cell security guards walked around the line, looking up and down the block for signs of trouble. “These T cells move around the epithelium as if they were really patrolling,” Kronenberg said.

But what makes these T cells work?

“We already understand why T cells enter the gut, but we need to understand what keeps them there, ” Kronenberg said. In fact, many immune cells persist in specific tissues for a long time. By understanding the signals that keep T cells in certain tissues, Kronenberg hopes to shed light on diseases such as inflammatory bowel disease, in which too many inflammatory T cells accumulate in the gut.

In new study, researchers found that important signals in the gut are sent through the basement membrane, which is the upper A thin layer of protein under the skin. In a nightclub scene, the basement membrane is the sidewalk and everyone is standing.

Their experiments showed that epithelial cells can stimulate the synthesis of basement membrane proteins through the HVEM protein on their surface. The team found that without HVEM, epithelial cells cannot function because they produce less collagen and other structural components needed to maintain a healthy basement membrane.

T cells detect the basement membrane through the adhesion molecules (called integrins) they express on their surface. The interaction of T cell integrins with basement membrane proteins facilitates the messages that enable T cells to survive and patrol epithelial cells. It’s as if epithelial cells have written messages on the sidewalk: “Stay here,” “Patrol here,” “Do your job.” Without enough basement membrane, T cells cannot survive or continue patrolling.

Using a mouse model, the researchers then showed that removing HVEM expression only in gut epithelial cells is healthy for the gut major blow. The patrolling T cells also didn’t survive, and they didn’t move as much. These T cells make terrible security guards. When attacked by Salmonella typhimurium, an invasive bacteria that causes gastroenteritis, the T cells allow the infection to take over the gut and spread to the liver and spleen. Thus, HVEM from epithelial cells sets the stage for T cells to protect the gut – which is why they survive in epithelial cells – to communicate indirectly with T cells through the basement membrane.

These insights come from a series of studies spearheaded by study lead author Dr. Goo-Young Seo, LJI lecturer and Dr. Daisuke Takahashi The experiment, formerly at LJI, is now at Keio University in Tokyo. The team worked closely with the laboratory of LJI Professor Dr. Hilde Cheroutre, the LJI Microscopy Core, the LJI Flow Cytometry Core, and employed in vivo imaging RNA-sequencing techniques to study the role of HVEM in the gut.

Looking ahead, Kronenberg and his colleagues are interested in studying the role of HVEM in maintaining a healthy gut microbiome. There are indications that a lack of HVEM affects the composition of the gut microbiome, even in the absence of pathogenic bacteria, Kronenberg said.