monocytes

Unusual growth in an immune cell class called myeloid cells is evident in the bone marrow of people with multiple sclerosis (MS), and these cells likely contribute to the inflammation that drives the disease, according to a new study. Experiments in mice suggest that myelin-reactive T-cells can migrate to the bone…

Lipid (fat) molecules can function as chemical couriers, taking messages from tissue to tissue, organ to organ as part of the body’s immune defense guidance system. But in certain diseases such as multiple sclerosis (MS), the courier service may go awry. One such lipid molecule, called sphingosine 1-phosphate (S1P),…

Extracellular vesicles (EVs), tiny sacs released from myelin-producing cells called oligodendrocytes, may help dampen the immune system’s attack against myelin, whose loss is the hallmark of multiple sclerosis (MS), a new mouse study shows. The findings suggest that oligodendrocytes-released EVs could work as an universal immunotherapy for MS…

Lowering levels of a protein called reelin — which regulates how permeable blood vessels are to immune cells — reduced infiltration of these cells into the central nervous system (CNS), preventing neuroinflammation and disease progression in a mouse model of multiple sclerosis (MS). These data, which also showed that Reelin…

Targeting the MOSPD2 protein may prevent immune cells known as monocytes from entering the central nervous system (CNS), which may significantly ease brain inflammation and myelin damage in multiple sclerosis (MS), a study in mice suggests. VBL Therapeutics, the company leading the study, has developed…

Altered levels of molecules important for cell regulation — called microRNAs — have been found in specific immune cells isolated from the blood of people with multiple sclerosis (MS), a study reveals. These immune cells, called monocytes, transform into macrophage cells,…

A subset of monocytes (a type of immune cells) that can infiltrate the central nervous system and drive nerve cell damage in multiple sclerosis (MS) may be a better target for preventing disease progression than the cells of the immune system that are currently targeted with MS therapies,…

A link between fat molecules called ceramides and worsening disease in overweight and obese people with multiple sclerosis appears to exist, a study reports, with its findings suggesting that ceramides prompt the growth of immune cells called monocytes, which in turn spurs disease progression. These results also strengthen the likelihood that lifestyle factors, like diet and weight, can act as disease modifiers, its researchers said. High body mass index has been linked to the risk of developing MS, but for reasons that aren't clear. One idea is that weight-induced differences in lipids (fat molecules) in the blood, because they are involved in several cellular signaling processes, may affect MS and its course in people with higher BMIs. To test this hypothesis, a team led by researchers at the Advanced Science Research Center (ASRC) at The Graduate Center and at the Icahn School of Medicine at Mount Sinai analyzed 54 patients with relapsing-remitting MS (MS), ages 18 to 60, and with normal or high BMIs (27 people in each group). Participants were followed for two years. BMI is a measure of body fat based on height and weight. A normal BMI is defined as one between 18.5 and 24.9, while a person is considered overweight with a BMI of 25–29.9, and obese it is 30 or higher. Researchers took blood samples, and looked for differences between the groups in terms of both immune cells and blood lipid profiles. They then validated their findings in a separate group of 91 RRMS patients. Patients with high BMIs tended to have more monocytes than those with normal BMIs. Monocytes can travel through the blood to tissues where they develop into macrophages, immune cells with various functions that are best known for "eating" invading bacteria. Monocytes can also travel to the brain and damage nerve fibers. Overweight and obese patients also had significantly higher levels of ceramides compared with normal-weight patients, and the researchers wondered if a link might exist between the two. Through a set of experiments in cells, they discovered that ceramides cause epigenetic changes in monocytes; that is, they alter the way their genomes are "read," so they alter gene activity. Specifically, ceramide-treated cells showed a type of epigenetic change called methylation — which generally turns genes "off" — in genes that normally help prevent cells from dividing. Conceptually, these genetic changes serve to unleash monocytes, leading them to grow more (proliferate) than they otherwise might. The researchers also found more methylation on the genomes of monocytes from high-BMI patients than those from low-BMI patients, and they noted that the overweight or obese patients also tended to have greater disease activity, worse disability progression, and more brain lesions on MRI (magnetic resonance imaging) scans on follow-up. Finally, the researchers tested a mouse model of MS, giving one group of mice a standard diet and another a high-fat diet. Mice fed the high-fat diet were found to have greater disease severity, more brain lesions, and more monocytes, confirming the findings seen in MS patients. "This study gives us a much-needed view into the environmental influences that can affect and change the behavior of cells in an individual's body," Kamilah Castro, the study's first author, said in a press release. "Our findings suggest that increased levels of saturated fat as a result of dietary habits are one likely cause of the epigenetic changes that advance MS, which gives us a starting point for a potential intervention." According to the team, the findings support the concept of nutri-epigenomics: that is, the ability of food to alter the way the genetic information is interpreted by each cell, and suggest that "weight management and dietary intervention" might affect MS prognosis. One limitation was the study's small size, its researchers noted. "While we consider our results … very exciting and mechanistic, we acknowledge that the potential consideration of ceramide levels as biomarkers for disease progression in MS would require validation ... using larger cohorts with a longitudinal and/or cross-sectional design," they concluded. "It will also be important to evaluate the effectiveness of dietary intervention (with an emphasis on the reduction of specific classes of saturated fats), as potential modulator of plasma ceramide levels and possibly of disease course in MS patients."

A cell therapy product derived from human umbilical cord blood cells may be a promising treatment approach for patients with demyelinating diseases, such as multiple sclerosis (MS) or leukodystrophy, according to a recent study developed at the Duke University Medical Center. The study, “A cord blood monocyte–derived cell…

In a recent study entitled “Myeloid cells as target of fingolimod action in multiple sclerosis,” a team of scientists investigated the impact of fingolimod (Gilenya, Novartis), an approved drug for multiple sclerosis (MS), on the reactivity of myeloid cells, a key group that comprises several immune cells that…

In a new study entitled “Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation,” a team of scientists discovered the mechanism by which autoreactive T cells are capable of penetrating a patient’s brain and induce multiple sclerosis. The study was recently published in the advance online issue…