Mysterious immune cells may trigger inflammation in multiple sclerosis and other brain diseases

According to a new study by researchers from the Weill Cornell School of Medicine and the New York Presbyterian Church, a group of immune cells can prevent gastrointestinal inflammation under normal conditions, but is associated with multiple sclerosis (MS) and other brain inflammations.
The opposite effect may be produced in disease
.

The researchers published their findings in the journal Nature on December 1, 2021, when they were studying a type of immune cell called group 3 innate lymphocytes (ilc3), which helps the immune system tolerate Beneficial microorganisms, and inhibit inflammation of the intestines and other organs throughout the body
.

Scientists call this subset of inflammatory ILC3s and found that they model the state of the central nervous system in mice instead of suppressing the immune response.

"This work has the potential to help us understand and treat a variety of conditions involving T cell infiltration," said senior author Dr.
Gregory Sonnenberg, a medical microbiologist in gastroenterology and hepatology.
And associate professor of immunology, and a member of the Jill Roberts Institute of Inflammatory Bowel Disease at Weill Cornell School of Medicine
.

Multiple sclerosis affects more than 2 million people worldwide
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Researchers have found in recent studies that ilc3 in the intestines acts as a sentinel and immunomodulatory factor, which can inhibit inflammation, including inflammatory T cell activity, and can also prevent cancer
.

The researchers showed that in the mouse model of the lady, these inflammatory ILC3s brain functions as antigen presenting cells": They showed the main component of myelin protein, the insulating layer around nerve fibers, and the myelin T cells-prompting them to attack and cause disease signs of nerve damage
.

"The penetration of these inflammatory ILC3s into the brain and spinal cord of mice is consistent with the onset and peak of the disease," said first author John Benji Grieg, who is the laboratory of Sonnenberg at Will Cornell University.
Doctoral student of the Graduate School of Medical Sciences
.

Researchers found that they can prevent MS-like diseases in animals by removing a key molecule called MHCII from ilc3.
This molecule is usually used in the antigen presentation process.
Removing MHCII essentially prevents cells from activating and attacking the marrow.
The ability to sheath T cells
.

"Although we have the best disease-modifying therapy for multiple sclerosis, the patient's condition continues to develop, and because of the early onset of the disease, they face the prospect of permanent physical and cognitive disability," Professor of Neuroscience Dr.
Tim Vartanian, co-author, said Feil Family Brain and Thinking Institute Weill Cornell Medical Division Chief Multiple Sclerosis and Neuro-immunology Neurology and Neurology Professor at New York Presbyterian Hospital/Will Cornell Medicine and Weill Cornell Medical Center
.

Finally, the researchers found that ilc3 in other tissues in the body can be programmed to effectively combat the activity of T cells infiltrated in the brain, thereby preventing MS diseases in mice
.

This work was done in close collaboration with Dr.
Ari Waisman, Director of the Institute of Molecular Medicine at the Johannes Gutenberg University Medical Center in Mainz.
Based on previous studies, the researchers proved that there is ilc3 in the intestine, which is slightly different.
In order to promote the inactivation or "tolerance" of T cells, the antigen is displayed to T cells in a way
.
Researchers have demonstrated through experiments that by exposing these tolerance-inducing intestinal ilc3 to myelin, they can prevent neuroinflammatory T cell activity and the development of ms-like diseases in mice
.

Dr.
Sonnenberg said that this work therefore points to the possibility that one day, by directly inhibiting the activity of inflammatory ilc3 that infiltrates the brain, or by targeting autoantigens to intestinal ilc3 that promotes tolerance to other tissues, it can be treated.
Multiple sclerosis and many other potentially inflammatory diseases
.

references:

"Antigen-presenting innate lymphoid cells orchestrate neuroinflammation" by John B.
Grigg, Arthi Shanmugavadivu, Tommy Regen, Christopher N.
Parkhurst, Anees Ahmed, Ann M.
Joseph, Michael Mazzucco, Konrad Gronke, Andreas Diefenbach, Gerard Eberl, Timothy Vartanian, Ari Waisman and Gregory F.
Sonnenberg, 1 December 2021,  Nature .

DOI: 10.
1038/s41586-021-04136-4