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Immune cells ‘guided’ by our microbiota

Recherche dans le laboratoire de Sebastian Amigorena, porteur du projet Centre d’immunothérapie de l’Institut Curie, dans le cadre du projet d’établissement 2015-2020.

Intestinal microbiota is thought to control the development of some lymphocytes in the thymus, according to research conducted by Olivier Lantz, head of the CD4 lymphocytes, innate T cells and cancer team at Institut Curie’s Research Center, and François Legoux, one of the team’s researchers. A new piece of the puzzle in understanding the immune system, which may prove crucial in treating inflammatory digestive disorders and colon cancer.

In a study published in Science, François Legoux and Olivier Lantz, from l’Equipe lymphocytes CD4+, lymphocytes T innés et cancer (U932 Immunité et cancer / Institut Curie ) showed that some T cells, recognizing a bacterial product known as 5-OP-RU, need intestinal bacteria in order to develop in the thymus. Their work shows that some of the intestine’s bacteria secretes 5-OP-RU, which then travels through the body to the thymus, where it is trapped and presented to immature T cells. In response, the T cells that recognize the 5-OP-RU mature, increase in number and leave the thymus for the mucous membranes, and the intestine in particular. T cell ‘training’ in the thymus is therefore governed by microbiota molecules, a fact that challenges everything we thought we knew, and suggests that microbiota is an integral part of the immune self.

Critical issues

In the intestine, the T cells that recognize 5-OP-RU strengthen the epithelial barrier, thus encouraging healthy coexistence with microbiota. Understanding the interactions between our immune system and our microbiota is key, because their malfunctioning is linked to a number of illnesses and disorders. The T cells reinforce intestinal flora by restricting damage caused by bacteria – even symbiotic damage”, explains François Legoux. “Inflammation and disorders (such as Crohn’s disease, colitis, inflammatory bowel diseases, obesity and diabetes) linked to disruption in this symbiosis can occur. These T cells that have been trained by microbiota play an important role in all these disorders. There’s still a lot of work to be done in this area, but the crucial point is gaining a better understanding of how this symbiosis operates”.

This research’s findings seem highly promising. Working with this symbiosis could ultimately improve treatment for colon cancer and inflammatory digestive diseases, and help increase our understanding of how diabetes and obesity occur.

The human body contains around 39,000 billion bacteria, and major research efforts have been made in an attempt to better understand this symbiotic coexistence. In particular, the way in which the organism’s bacterial flora interacts with our defense system, the immune system, remains poorly understood. T cells play a key role in the immune system. They are produced in the thymus (hence the ‘T’), where they are trained to recognize and fight off foreign bodies in our organism over the course of our lifetimes. During their ‘training’, T cells likely to attack the body’s cells are eliminated, thus preventing autoimmune diseases. The thymus is therefore seen as the place where the immune system distinguishes between the self and the non-self.