Researchers probe gut microbiome, MS connection

julio 28, 2023
New findings suggest that auto-aggressive T cells are activated in a specific area of the intestinal canal – and that activation is microbiome-dependent. Researchers said their results make an important contribution to better understanding the development of multiple sclerosis and potentially open up new therapy options in the long term.

MS is an inflammatory autoimmune disease of the central nervous system. It is triggered by certain T cells, which infiltrate the brain and spinal cord and attack the insulating myelin sheath around axons. In recent years, researchers have found mounting evidence that the gut microbiome plays a substantial role in the activation of these cells. However, the precise location and the underlying mechanisms remained unclear. Using imaging techniques in a mouse model, a team of researchers from Ludwig-Maximilians-Universität, in Munich, Germany, managed to track the microbiome-dependent activation of the cells live.

For their study, the scientists used two-photon imaging for live visualization of the mobility and activation of specific T cells. With a sensor protein, they recorded changes in cellular calcium concentration, allowing them to draw inferences about the activity of the T cells. The encephalitogenic T cells – T cells that can cause inflammation in the brain – investigated by the researchers specifically target a protein in the myelin sheath around neurons and play a key role in the development of MS.

Researchers demonstrated that the essential part for activation of these cells takes place in the so-called gut-associated lymphoid tissue, which is located in the mucous membrane of the gut – more precisely in the lamina propria, a connective tissue layer of the small intestine. However, this only happened when the mice had an intact intestinal microbiome: If the gut was microbe-free, activation did not occur. The researchers noted that activation in the lamina propria seems to be a general mechanism, even for nonencephalitogenic T cells, which target other molecules in the body. 

They found that activation depended on the microbiome. The scientists hypothesize that the microbiome produces molecules that are recognized by the respective receptors in the T cells and activate the cells in this way. In encephalitogenic T cells, the activation turns on genes such that they differentiate into so-called Th17 cells. Through this differentiation, the cells develop the properties that enable them to migrate into the central nervous system and trigger inflammation. 

Results of animal model studies sometimes do not translate to humans and may be years away from providing a marketable treatment.
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