Discovery offers new path for multiple sclerosis treatment

The newly-found communication link between brain cells and immune cells might offer a new way to combat multiple sclerosis.
John Loeffler
Nerve cell attacked by antibodies
Nerve cell attacked by antibodies 

Multiple sclerosis is a debilitating disease that afflicts nearly 3 million people worldwide. While there is no cure for the disease, researchers at Mount Sinai Hospital and the Mount Sinai School of Medicine believe they have uncovered a new approach for possible treatments in the future.

In a new study published in the journal Immunity, researchers describe how crosstalk between certain brain cells and peripheral immune cells can increase inflammation in the brain and contribute to MS pathology. The key inflammatory protein involved, interleukin-3 (IL-3), has been seen coordinating this cellular communication and so provides a possible treatment vector to reduce the severity of symptoms for those living with MS.

“While we’ve known that brain cells and immune cells are important to multiple sclerosis, the pathways or proteins that act as messengers to mediate communication between these disparate cell populations are poorly understood,” the study's senior author Cameron McAlpine, Ph.D., Assistant Professor of Medicine (Cardiology), and Neuroscience, at the Icahn School of Medicine at Mount Sinai, said in a statement. “We’ve identified a previously unknown biological pathway in MS involving IL-3 as a mediator of cross-talk between brain and immune cells and an important regulator of brain inflammation.”

MS is a chronic inflammatory disease affecting the body's nervous system, especially the brain and spinal cord, that can create episodic disability lasting anywhere from days to weeks and progressively worsens over time. There is no cure for MS, which can eventually lead to paralysis and early death, so treatment in the early stages of the disease can hopefully lead to better outcomes later in life.

IL-3 has been tied to multiple disorders ranging from Alzheimer's to many autoimmune disorders, but its impact on brain function has not been extensively studied.

How the study was carried out

The researchers used both human samples and testing in mice to study the role IL-3 might play in the development and progression of MS. Analysing samples of human cerebrospinal fluid from 29 healthy participants and 36 participants with MS, the researchers found that the latter had elevated levels of IL-3. Using the mouse models, researchers then identified the types of brain cells, astrocytes, and infiltrating immune cells (T cells) responsible for producing IL-3. They also found that certain other brain cells respond to the presence of IL-3 by expressing an IL-3 receptor known as IL-3Ra.

When IL-3 and IL-3Ra are deleted, brain inflammation noticeably declines, and the mouse experienced an improvement in its MS symptoms. Using these data, researchers returned to 12 human participants, six without MS and six with MS, and performed single nuclear sequencing of brain cells.

“We found in the brains of MS patients the appearance of IL-3Ra-expressing myeloid cells, and evidence that these cells are programmed and wired for inflammation and immune cell recruitment, processes that are detrimental in MS,” lead author Máté Kiss, Ph.D., a postdoctoral fellow from the Cardiovascular Research Institute at Mount Sinai, said. “This is a critical finding because in MS patients, myeloid cell IL-3Ra expression and IL-3 levels in the cerebrospinal fluid correlate with worse brain inflammation and MS severity.”

By identifying this mechanism in MS patients, the researchers hope to develop what they've learned into a new therapeutic approach to MS.

“Biologics and small molecules targeting IL-3 signaling have been used in cancer therapy,” Dr. McAlpine said, “and our work suggests that this pathway could be therapeutically targeted to not only treat MS but other neuroinflammatory conditions like Alzheimer’s disease and dementia as well. However, further work is needed to formally test this.”

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