Researchers at Mount Sinai have made a significant discovery regarding the communication between brain cells and peripheral immune cells in the progression of multiple sclerosis (MS). Their findings, published in the journal Immunity, highlight a previously unknown pathway involving the inflammatory protein interleukin-3 (IL-3) that facilitates the interaction between the brain and immune system, leading to increased brain inflammation and worsening MS pathology.
MS is a chronic neuroinflammatory disease that affects approximately one million people in the U.S. Typically, symptoms appear between the ages of 20 and 40, and the disease progresses over time, resulting in impaired mobility, cognitive decline, paralysis, and premature death. Unfortunately, there is currently no cure for MS.
The role of IL-3 has been studied in various disorders, including Alzheimer's disease, by the same team from the Cardiovascular Research Institute at Mount Sinai. However, its involvement in brain function has been inadequately explored.
In this study, the researchers utilized human samples and mouse models to investigate the role of IL-3 in MS pathophysiology. They found higher levels of IL-3 in the cerebrospinal fluid of MS patients compared to healthy individuals. Additionally, they discovered that astrocytes (resident brain cells) and T cells (infiltrating immune cells) were the primary sources of IL-3 in the central nervous system. The team also observed that microglia (another type of immune cell) and infiltrating myeloid cells responded to IL-3 by expressing its receptor, IL3-Ra. Deleting IL-3 or IL-3Ra led to reduced immune cell infiltration and inflammation, accompanied by improved MS symptoms in mice.
By analyzing brain cells from healthy individuals and MS patients, the researchers identified IL-3Ra-expressing myeloid cells in the brains of MS patients. These cells exhibited signs of inflammation and immune cell recruitment, which are detrimental in MS. Furthermore, the expression of IL-3Ra and IL-3 levels in the cerebrospinal fluid correlated with increased brain inflammation and MS severity in patients.
This novel mechanism sheds light on MS pathogenesis and suggests that targeting IL-3 signaling could be a promising therapeutic approach. Existing therapies that target IL-3 signaling have been used in cancer treatment, and this research indicates their potential application in treating MS, as well as other neuroinflammatory conditions such as Alzheimer's disease and dementia. However, further investigation is necessary to validate these findings and test potential therapeutic interventions.
Source: The Mount Sinai Hospital