Discovery of Immune Cell Subtypes in Mice is an MS ‘Breakthrough,’ Researcher Says

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by Jonathan Grinstein |

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Previously unknown immune cell subtypes are present in the inflamed brain of mice models of multiple sclerosis (MS), a new study reports.

According to the researchers, these subsets of myeloid cells (cells derived from hematopoietic stem cells in the bone marrow) can offer a strong basis for therapeutic targets in neuroinflammatory and autoimmune diseases.

The research article with this finding, “Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation,” was published in the journal Science.

Myeloid cells — a class of immune cells that contain various cell types such as macrophages, monocytes, and dendritic cells — in the central nervous system play critical roles in the initiation and worsening of MS.

In a MS mouse model, called experimental autoimmune encephalomyelitis (EAE), myeloid cells diversify into many different unknown subtypes of dendritic cells and monocytes (a type of white blood cell).

Yet, disease-specific immune cell subtypes that can trigger neuroinflammation in MS remain largely unknown.

To characterize cells that initiate and exacerbate MS, a team led by researchers from the University of Freiburg, in Germany, compiled an atlas of myeloid subsets in EAE mice under normal and inflammatory conditions.

They looked at individual immune cells during T-cell infiltration of the central nervous system — an important step in MS initiation.

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The team used microscopy and single cell sequencing technology to characterize cell subtypes by their size, shape, and RNA molecule content (RNA is the intermediate between the genetic information encoded by DNA and proteins). In addition, they studied different compartments of the nervous system to see if there were context-specific differences in immune cell types.

“These methods allow us to paint an entirely new cellular picture of very complex tissues like the brain,” Dominic Gruen, PhD, a study co-author, said in a press release.

The team found that nervous system-associated myeloid cells, called macrophages, replicate and expand their population. These macrophages randomly grew and divided into specific subtypes in different nervous system compartments during EAE.

“CNS [central nervous system]-resident macrophages quickly generated context-dependent subsets during disease,” the researchers wrote.

The team also found that different immune cells in the brain remain chronically activated in the course of the disease.

“This permanent activation of the immune cells could explain why the brain of an MS patient is chronically attacked over the course of years,” said Marta Joana Costa Jordão, the study’s first author.

Overall, Marco Prinz, PhD, medical director of the Institute of Neuropathology at the Medical Center -University of Freiburg, and the study’s senior author, concluded: “Our findings constitute a breakthrough for the understanding of autoimmune diseases like multiple sclerosis. We hope that it will now be possible to develop new, more cell-specific therapeutic approaches that are less prone to side-effects for treating inflammatory diseases like MS.”

“The main problem with the previous, inadequate therapy was that it inhibited the entire immune system. However, we succeeded in finding new subtypes of cells that are specific for local inflammation and destruction in MS. They might, therefore, be selectively inactivated,” Prinz said.

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