A protein called dedicator of cytokinesis 8 (DOCK8) is key for the development and expansion of self-reactive immune T-cells that wrongly attack myelin, a study in a mouse model of multiple sclerosis (MS) found.
DOCK8 drives the migration and stimulating capacity of dendritic cells — immune cells that ‘teach’ T-cells to attack a given target. Limiting migratory dendritic cells by manipulating DOCK8, or through other means, could be a way of restricting autoimmunity in MS, the research team said.
These findings were presented by Estelle Betteli, PhD, at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020, in West Palm Beach, Florida (Feb. 27–29). The presentation was titled “Lymphocyte-myeloid Cell Networks in MS.”
MS is caused by the immune system mistakenly attacking myelin, the insulating and protective protein coating of nerve fibers in the central nervous system (CNS; brain and spinal cord). Due to mechanisms still unclear, patients develop self-reactive immune T-cells that destroy myelin, and this is closely linked to CNS inflammation and nerve cell death.
Typically, for T-cells to launch a targeted attack, they first need to be “primed” by other immune cells. These are collectively known as antigen-presenting cells, including a group referred to as dendritic cells (DCs).
Dendritic cells are a heterogeneous family, with varied locations and behaviors, that act as ‘sentinels’ for the immune system, continuously sampling tissues to detect harmful microbes or other substances. They specialize in capturing an intruder’s proteins (antigens), and displaying pieces of them to T-cells so they know which targets to attack.
When dendritic cells detect foreign elements they quickly change their behavior, leaving the tissues where they reside and entering lymphatic vessels through which they migrate to lymph nodes. It’s here that they actively present antigens to T-cells.
In people with allergic or autoimmune conditions like MS, dendritic cells can incorrectly display pieces of proteins that are natural to a system — like myelin. In doing so, they prime T-cells to wrongly attack (self-react against) a person’s own cells and tissues.
We are sorry that this post was not useful for you!
Let us improve this post!
Tell us how we can improve this post?