In a new study, researchers from the University of Toronto, Canada, uncovered the process behind the formation and maintenance of tertiary lymphoid tissues (TLTs), structures found in the meninges in the brains of multiple sclerosis (MS) patients. Their findings, reported in the article “Integration of Th17- and Lymphotoxin-Derived Signals Initiates Meningeal-Resident Stromal Cell Remodeling to Propagate Neuroinflammation” and published in the journal Immunity, further understanding in the processes that drive the disease.
TLTs are structures similar to lymph nodes, but found within the outer membranes of the brain and spinal cord called the meninges. Scientists have previously observed that in the brains of MS patients, lymphocytes, a type of white blood cells, tend to accumulate in these structures, and they relate them to the typical neuroinflammation associated with progressive MS. The formation and molecular and cellular support of TLTs has been poorly elucidated so far.
The study led by Professor Jennifer Gommerman of the Department of Immunology at Toronto and conducted in an experimental autoimmune encephalitis (EAE) animal model, which mimics human MS, revealed that immune T helper 17 (Th17) cells induced robust TLTs within the brain meninges, associated with local demyelination.
Furthermore, Th17 cells were found to influence the organization of stromal cells (connective tissue cells). Scientists observed that Th17-cell-induced TLTs were supported by a complex network of stromal cells, which through production of extracellular matrix proteins and chemokines, enabled the lymphocytes to reside within the meninges, instead of allowing them to just pass through. Researchers noted that TLT structures developed through these molecular and cellular events were very similar to other lymphoid tissues, found in tonsils and lymph nodes.
“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,” Dr. Gommerman said in a press release.
Although not identifying TLTs as a definite cause of MS, the results clearly pointed to their role in MS pathology and could be explored for potential therapies, such as new drugs targeting Th17 cells.