How do Multiple Sclerosis drugs affect the Immune Synapse?

What is it about?

Multiple Sclerosis (MS) is an autoimmune disorder that affects the central nervous system. As in all autoimmune disorders, the immune system attacks parts of the human body; in MS the target of the attack is the myelin, i.e. the sheath that covers nerve axons. The attack is orchestrated by the cells comprising the immune system, mainly the B- and T- lymphocytes, which are part of the adaptive immune system, and microglia, dendritic and NK cells, which are part of the innate immune system. The drugs that are available for the treatment of MS today (called disease modifying drugs, DMDs) aim at modifying the properties of immune cells, in order to render the immune system less reactive against the patient’s own nervous system. Numerous studies published to date have assessed how DMDs affect the number of cells comprising each of the categories listed above. It is, however, necessary to also understand how they affect the interaction amongst different cell populations, which is an important step to mount an effective immune response. Some of these cells (B lymphocytes and dendritic cells, among others) are responsible to present foreign or self antigens to the T lymphocytes, thus acting as antigen presenting cells (APCs). T lymphocytes, when activated, attack myelin. Said interaction is called Immune Synapse and involves several different types of molecules. It is well established that activation of T lymphocytes requires two signals: one that arises from the interaction between the T cell receptor (TCR) with its cognate antigen presented by major histocompatibility complex (MHC) molecules expressed by APCs and another provided by the interaction of co-signaling receptors on T lymphocytes with their counter-ligands expressed on the surface of APCs. These co-signaling molecules can be either stimulatory or inhibitory and co-determine the ultimate fate of T cell activation. We systematically review how DMDs for MS affect the co-signaling and adhesion molecules that mediate the formation of immune synapses.

Featured Image

Photo by National Institute of Allergy and Infectious Diseases on Unsplash

Photo by National Institute of Allergy and Infectious Diseases on Unsplash

Why is it important?

Understanding how DMDs for MS affect the immune synapse can enhance our knowledge on the way they work, why they are effective and how they can be optimally positioned in the treatment journey of a patient. It can also guide the design of future MS drugs, able to modify the immune system in a more focused manner.