Last week, a study published in the prestigious journal Nature made waves in the scientific community with the discovery of a direct connection between the lymphatic system and the central nervous system (CNS). This finding was ground-breaking in that it provided concrete evidence that toppled the classically-held belief that the brain and spinal cord (together comprising the CNS) lacked lymphatic drainage and a direct link to the immune system, and unveiled a new avenue for exploring the disease-causing mechanisms of multiple sclerosis.
What is the lymphatic system, exactly? The lymphatic system is a network of vessels and organs in the body involved in both draining and filtering interstitial fluid (the fluid that bathes the cells of our tissues) back into the blood. In addition, the lymphatic system transports lymphocytes (a type of white blood cell) and antigen-presenting cells (APCs), which are both integral components of the immune system. During an infection, invading microbes are detected by APCs, which engulf the microbe and display pieces of them (called antigens) on their surface. The APCs travel to the lymph nodes (lymph organs distributed throughout the body) where they interact with lymphocytes that “recognize” the microbial antigen, causing the lymphocyte to activate and mount an immune response in order to fight the infection.
To date, the brain has been among a small handful of organs considered to be “immune privileged”; that is, antigens present in the brain were thought unlikely to trigger an inflammatory immune response, presumably due to the absence of lymphatic drainage. Although it has been increasingly evident that there is in fact much more interaction between the immune system and the CNS than we once thought, the mechanisms underlying this interaction have been poorly understood making it difficult to understand just how MS begins.
This new study, conducted by a group of neuroimmunology researchers at the University of Virginia, have discovered the presence of functional lymphatic vessels lining the dural sinuses (compartments in the brain filled with cerebrospinal fluid that bathes and protects the tissues of the brain) in both mouse and human brain tissues. These vessels drain into the deep cervical lymph nodes in the neck, thus providing the first direct link between the CNS and the lymphatic system and a means for the movement of immune cells between these two systems.
So what does this mean for MS? Although it’s too early to say for sure, these findings could open up new opportunities for studying the disease mechanisms by which the body’s immune system turns against its own tissues in MS. It’s been known for some time that myelin antigens displayed by APCs have turned up in lymph nodes throughout the body (where they interact with lymphocytes and prime them to become reactive against myelin) in people living with MS. This in turn leads to the cascade of immune events called epitope spreading whereby inflammatory destruction of tissue in the CNS releases new antigens that are presented to lymphocytes in the lymph nodes and primes immune responses against them. However, how these myelin antigens leak out of the CNS has been something of a mystery.
The newly discovered lymphatic drainage system from the CNS complements other demonstrated pathways by which immune cells move freely between the CNS and the periphery, notably the disruption of the blood-brain barrier that has been the subject of intensive study (for instance, in this recent MS Society-funded study by Dr. Alexandre Prat and colleagues). Whether this discovery will translate into a new therapeutic target for suppressing or preventing the autoimmune response in people with MS remains to be seen; in the meantime, we’ll be keeping an eye on these developments and keeping you informed.
Louveau A et al. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature. doi: 10.1038/nature14432
Image credits: National Institutes of Health