New step toward determining the cause of multiple sclerosis

MS is a disorder in which the immune system attacks the brain. It has no known cause and no cure. Normally, immune responses are triggered in lymph nodes and other lymphoid organs to protect us from a virus or pathogen. However, scientists have observed that a type of white blood cell known as lymphocytes can sometimes congregate into so-called "tertiary lymphoid tissues (TLTs)" in the brain of MS patients. These structures are similar to lymph nodes, but are found within the outer membrane of the brain -- known as the meninges. They often coincide with the appearance of tell-tale brain inflammation associated with progressive MS. But how the TLTs are formed and what keeps them there has been unclear.

The U of T researchers, led by Professor Jen Gommerman of the Department of Immunology, discovered that TLTs were created by the presence of stromal cells, which are specialized cells that produce an intricate network of fibres. They can effectively create a net, which once formed, become a gathering place for a type of T cell known as T helper 17 cell (or Th17).

"While T cells are an important part of the body's ability to ward off infection and disease, in autoimmune disorders, they can mistake healthy tissue for potential threats and respond by lashing out, causing damage. The team observed that this Th17 response resulted in the type of brain tissue inflammation associated with MS," says Gommerman.

More than that, the Th17 cells could also influence how the stromal cells organized. The resulting structure that developed was remarkably similar to normal lymphatic tissue, such as you might find in your tonsils or lymph nodes in your neck.

Gommerman says this research, which was conducted using animal modeling, doesn't deliver a definitive answer to what causes MS, but it does appear to be a "smoking gun" associated with MS pathology. With further research, it may point to potential treatment options, such as targeted Th17 blockers.

The lead author of the paper, Natlia Pikor, recently completed her PhD under Gommerman's supervision. This project is part of a larger initiative exploring B cells in MS, which is supported by a team grant from the MS Society of Canada and affiliated Multiple Sclerosis Scientific Research Foundation. With Gommerman, it includes fellow primary investigators, neurologists Professor Amit Bar-Or at McGill University and Professor Alexandre Prat at l'Université de Montréal.