Immunology

Researchers at Institut Hospital del Mar d'Investigacions M-diques (IMIM) in Barcelona, in collaboration with the Icahn School of Medicine at Mount Sinai in New York and other U.S. Institutions, have found that intestinal mucus not only acts as a physical barrier against commensal bacteria and dietary antigens, but also prevents the onset of inflammatory reactions against these agents. This fundamental property of mucus was unknown until now and its discovery could potentially improve the life of people suffering from inflammatory bowel disease.

Mucus is a colloidal gel produced by glands present in our mucosal surfaces, including the intestine. "Our body produces on average a liter of mucus every day. Despite its abundance, mucus has been poorly studied and thus very little is known about its composition, synthesis and functional properties. Part of the problem may be that mucus is traditionally viewed as a symbol of disease and thus represents an antivalue" explains Dr. Andrea Cerutti, ICREA Research Professor, coordinator of the research group in B Cell Biology at IMIM, Professor of Medicine at Mount Sinai and responsible for the study. "In addition, mucus is fundamentally ambiguous. Its fluidity exists in slow motion and there is sticky thickness in its liquidity. This ambiguity may have conditioned a depreciatory estimate of the value of mucus by physicians, who have often put forth every effort to brush, wash or dissolve away mucus as if it were an evil thing" adds Dr. Meimei Shan, the first author of the study and a collaborator of Dr. Cerutti at Mount Sinai in New York.

"Immunologists have always been interested in finding out why we do not develop an inflammatory reaction to the trillions of bacteria and large amounts of food antigens that come in contact with our intestinal mucosa. Yet, these same agents cause dangerous inflammatory reactions and even death when other parts of our body are exposed to them. The discovery published in this study helps to explain this long-standing question." explains Maurizio Gentile, a PhD student in Dr. Cerutti's lab and major contributor of this work.

The building block of gut mucus is the mucin MUC2. This molecule not only acts as a physical barrier, but also provides anti-inflammatory signals to dendritic cells, which is an immune cell type that regulates the health of our intestine and helps us to fight against bacteria and food antigens. Dr. Cerutti's team used complex techniques involving cellular immunology and molecular biology to describe this process. "By showing the beneficial anti-inflammatory activity of mucus, our work opens up a broad field of research. The natural pharmacological properties of mucus might provide a promising complementary way to treat inflammatory bowel disease, including ulcerative colitis and Crohn's disease" comments Dr. Linda Cassis, another member of the team involved in this research. A collaborator of Dr. Cerutti at IMIM, Dr. Anna Bigas, was instrumental to define a transcription factor of the anti-inflammatory signaling pathway activated by MUC2 in dendritic cells.