In the early stages of inflammation, myeloid cells traffic to the sites of infection and inflammation to exert their effector functions such as the release of reactive oxygen species and cytokines. Although these products have anti-bacterial functions and can be regarded as beneficial, they also exert harmful effects to the surrounding tissue. This can be particularly observed in autoimmune diseases, including rheumatoid arthritis and multiple sclerosis (MS).
MS can be induced in mice by immunization with a central nervous system-specific peptide, leading to experimental autoimmune encephalomyelitis that reflects many aspects of MS in humans.
My doctoral research focuses on myeloid cells such as monocytes and dendritic cells, and how these cells respond during this autoimmune inflammation, particularly in the above-mentioned mouse model. I aim to understand what drives these cells to cause damage in the central nervous system and how we could alleviate the destructive programming of these cells. To study this, I examine their surface proteins, transcriptomics, and epigenetic programming.
The body’s defence mechanisms: innate and adaptive immunity
A few words about the immune system: the immune system is the body’s defence mechanism; it protects us from harm, such as bacteria and viruses. The immune system can be divided into two main branches: innate and adaptive immunity.
The innate immune system fights pathogens rapidly and effectively upon first contact. It acts as the body’s first line of defence and includes cells such as monocytes, neutrophils, Natural Killer cells, and dendritic cells.
The adaptive immune system on the other hand includes B and T cells, which protect the body through a specific and memory-based mechanism. These cells “remember” previously encountered pathogens and can therefore respond efficiently when they reappear. This reaction typically takes around 8-10 days to develop and is highly specific.
When the defence turns against the body
In multiple sclerosis, the body’s own immune defence attacks the tissues of the central nervous system. This leads to tissue damage, which in turn causes nerve cell injury and neurological symptoms, including the typical paralysis.
In the past decades, MS research has focused on the role of lymphocytes and how they harm the central nervous system. The earlier assumption was that T cells were mainly responsible for the destruction of the myelin sheaths surrounding nerve fibers and thereby impairing the transmission of the nerve impulses, resulting in MS symptoms. However, recent mouse studies have shown that T cells are not the primary cell type responsible for tissue damage. Instead, the destructive role appears to be carried out by myeloid cells. Additional experiments have demonstrated that when monocytes are depleted during autoimmune inflammation, the animals do not develop MS-like symptoms.
Why is this important?
While previous experiments have shown that monocytes mediate tissue damage, it is not known how they carry out the detrimental functions. Our research aims to provide valuable insights into the activation of myeloid cells during autoinflammatory immune reactions and to identify pathways that can be therapeutically targeted to suppress the immune response without affecting other cells of the immune system. This will advance our understanding of the complex interplay between myeloid cells and the immune system and could lead to the development of novel therapies for autoinflammatory diseases.
Hans Bergman
The author has a master’s degree in Cell Biology and is a PhD candidate in Molecular Medicine. He is interested in using new technologies to better understand the “self-destructive” behaviour of myeloid cells during autoimmune disease such as MS.
