SLAM4 receptor�??s role in intestinal immunity characterized 

Reuters Health Information: SLAM4 receptorâ??s role in intestinal immunity characterized 

SLAM4 receptorâ??s role in intestinal immunity characterized 

Last Updated: 2017-05-19

By Marilynn Larkin

NEW YORK (Reuters Health) - The signaling lymphocyte activation molecule family member 4 (SLAM4) is a marker of intestinal immune cells that helps protect against enteric pathogens, researchers say.

Because the gut is exposed to the environment, it is constantly at risk of infection from pathogenic organisms. To protect itself from infection, the mucosal immune system must induce inhibitory molecules to maintain homeostasis while remaining prepared to activate pathways for a quick attack, according to Dr. Yasminah Laouar of the University of Michigan School of Medicine in Ann Arbor and colleagues.

“However,” they write in Gut, online May 9, “the signaling molecules by which the gut immune system generates these simultaneously activating and inhibitory pathways, to switch between homeostatic, often immunosuppressive and barrier-protective, function and potent active immunity are not fully understood.”

Natural killer cell receptors, including SLAM 4 (also known as CD244 and 2B4), are believed to be among the activating molecules, as the natural ligand for SLAMF4 is CD48, and in vitro engagement of SLAMF4 by CD48 induces cytotoxicity and cytokine secretion by human and mouse NK cells, according to the authors.

To investigate how SLAMF4 is acquired in the gut and, more specifically, what it contributes to intestinal immunity, the team examined SLAMF4 expression in samples from three types of genetically altered mice and from humans.

After multiple experiments, they determined that SLAMF4 is a selective marker of intestinal immune cells in both mice and humans; that it contributes to protection against enteric pathogens; and that it is induced directly in the intestinal mucosa, without involvement of any gut-associated lymphoid tissue.

More specifically, key contributors to SLAMF4 induction include bacterial products of gut anaerobes as well as gut-resident antigen-presenting cell TNLG8A.

In addition, inhibiting SLAMF4 expression makes mice more susceptible to oral infections, culminating in premature death.

“The discovery that gut symbiotic bacteria induce intestinal immune cells with the SLAMF4 receptor exemplifies host-microbe communication within the intestine and further supports the importance of a balanced gut microflora biodiversity in host immune functions,” the authors write.

Therefore, they suggest, “prescribing oral antibiotics to patients, particularly those who are immunocompromised, has to be carefully weighed.”

Dr. Mahmoud Ghannoum, director of the Center for Medical Mycology at University Hospitals Cleveland Medical Center and Case Western Reserve University in Ohio, said the study “clearly demonstrates that the microbial communities residing in our digestive system influence our immune response through communication channels within the gut.”

“Consequently,” he told Reuters Health by email, “maintaining the microbial balance and diversity will impact our health and wellness.”

“Having said that,” he added, “it is important to stress that studies into the underlying mechanisms - for example identifying what microbial products (metabolites) facilitate this communication - are needed to be able to translate these findings into therapeutic approaches.”

Gastroenterologist Dr. Saurabh Mehandru of the Icahn School of Medicine at Mount Sinai in New York City told Reuters Health by email, “This marker is one of a few receptors expressed on cells of the intestine that may affect the function of the intestines and are worth pursuing in clinical samples to understand clinical implications.”

“Caveats are that these are early studies and need validation in the human setting,” he concluded.

The authors did not respond to requests for a comment.

SOURCE: http://bit.ly/2rzUF4E

Gut 2017.

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