T-cells

A signaling molecule of the immune system called interleukin 13 (IL-13) may modulate the function of key immune cells involved in multiple sclerosis (MS), and their migration through the barrier that protects the brain and spinal cord. IL-13 is an “attractive molecule” and a potential avenue for treating MS,…

Ozanimod — an investigational oral therapy up for approval to treat relapsing multiple sclerosis (MS) — lowers the number of white blood cells circulating in the blood, supporting its ability to ease inflammation in the brain and spinal cord. But this treatment also does not affect all…

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’…

High-dose vitamin D supplements appear to aggravate inflammation and myelin loss in the brain and spinal cord, and worsen the disability associated with multiple sclerosis (MS), a study in a mouse disease model reported. Excessive use of vitamin D causes calcium levels to…

Immune system cells can either trigger or suppress inflammation by controlling mitochondrial respiration — the process that occurs in mitochondria, the cells’ powerhouses, and results in the production of usable energy by cells — according to a recent study. This discovery raises the possibility that…

A bone marrow transplant can remove the majority of overactive immune T cells from the central nervous system (CNS) in patients with active relapsing-remitting multiple sclerosis (RRMS), allowing the body to replace them with healthy ones, a study has found. This opens up new treatment avenues to…

Treating people with relapsing-remitting multiple sclerosis (RRMS) for one year with the immune-modulating therapy Gilenya (fingolimod) reduced the numbers of antibody-producing B-cells and of T helper cells, a study finds.  While the…

The immune signaling molecule interleukin-17A (IL-17A) promotes the recruiting of inflammatory cells to the central nervous system (brain and spinal cord) in a multiple sclerosis (MS) mouse model, a study found. The findings support the potential of therapies that target IL-17 in MS. IL-17A is part of the IL-17…

Changing a person’s diet to reduce the amount of methionine (amino acid found in food) could delay the development and progression of inflammatory and autoimmune disorders, including multiple sclerosis (MS). That finding was described in the study “…

People with multiple sclerosis (MS) have a more diverse set of immune cells in their cerebrospinal fluid (CSF), the fluid that bathes the central nervous system, but no such diversity is seen in their blood, a study reports. Instead, MS causes changes in the activation of immune cells in…

Mayzent (siponimod), an approved oral therapy for active secondary progressive multiple sclerosis (SPMS), promotes a more regulatory immune system, which may explain its added benefits for SPMS, new clinical data show. The study “Siponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosis” was published in the…

Probiotics show potential to prevent and delay the development of multiple sclerosis (MS) by changing immune and inflammatory responses, according to a review study. Data further support the link between the gut’s microbial community (microbiota) and the central nervous system (brain and spinal cord), and neurodegenerative diseases. However, large-scale clinical…

A signaling protein (Smad7) that usually blocks the activity of a molecule called transforming growth factor-beta (TGF-β) appears to be overactive in people with multiple sclerosis (MS), leading to the activation and migration of immune cells from the intestine to the central nervous system, a study reports. The study,…

A protein involved in cell metabolism, called PKM2, was found to be central to switching ‘on’ immune cells that play critical roles in inflammatory and autoimmune diseases such as multiple sclerosis (MS), an early study reports. Blocking the activity of PKM2 (pyruvate kinase M2) eased MS-like symptoms…

The transcription factor family AP-1 is crucial for the proper activation of immune T-cells, a new study shows, and this finding may have important implications for autoimmune diseases such as multiple sclerosis. The study, titled “AP-1 activity induced by co-stimulation is required for chromatin opening during…

Targeting the chemokine receptor CXCR6, a protein at the surface of a certain group of T helper cells, prevented the development of multiple sclerosis (MS) in a mouse model of the disease, a study reports. Its findings suggest that antibodies targeting T helper cells — known drivers of MS —…

A specific type of immune cell in a particular activation state is linked to such immune diseases as multiple sclerosis (MS) and inflammatory bowel disease (IBD), a collaborative research study found. Disease-associated genetic variants — changes in DNA sequences or mutations in genes — can affect the response of immune…

Brain inflammation in multiple sclerosis (MS) hijacks immature myelin repair cells, not only preventing myelin restoration but also promoting sustained inflammation and immune attacks against myelin, a preclinical study shows.

Scientists may have found a way to manipulate T-helper 17 (Th17) cells so as to lower their ability to trigger inflammation, delaying the onset of multiple sclerosis (MS) in a mouse model and slowing its progression without affecting the entire immune system. Their findings may lead to new treatments with fewer…

Females of certain species — like humans and mice — have a known ability to produce more of the gene Kdm6a than males because it’s located on the X chromosome, of which females have two. Kdm6a is also quite active in immune system T-cells, a study found, and silencing it in a mice model…

Though known mainly for killing tumor and virally infected cells, a T-cell subtype may restrain immune responses and be protective in autoimmune diseases such as multiple sclerosis (MS), according to new research. The study, “Opposing T cell responses in experimental autoimmune encephalomyelitis,” was published recently in…

Scientists identified and “fingerprinted” a group of T-helper cells that are unusually numerous in the blood and central nervous system of people with relapsing-remitting multiple sclerosis (RRMS), and may be the reason behind the neuroinflammation seen in these patients. This T-cell population carries specific markers involved in the transmission…

Gut microbes prime immune cells called microglia to protect the brain and nervous system from neurological damage due to viral infections, according to new research in mice. The findings suggest that maintaining a healthy and diverse microbiota — the population of bacteria, fungi, and viruses within the body, especially the…

Targeting a protein found in immune T-cells called Oct1 may help prevent the misguided immune response seen in autoimmune diseases like multiple sclerosis (MS), a study shows. Most importantly, a lack of Oct1 does not influence the immune system’s ability to fight viral infections. The study “T cell-selective…

An experimental treatment known as OB-002, that works to block an inflammatory molecule in the brain, prevented the development of lesions there after an early-in-life viral infection in a mouse model of multiple sclerosis (MS). The research “Brain-resident memory T cells generated early in life…

The loss of immune B-cells, and the resulting changes in the profile of immune T-cells, is a major mechanism of action for the beneficial effects seen with ublituximab treatment in multiple sclerosis (MS) patients, a study suggests. B-cells are a type of immune cell best known for producing…

Aubagio (teriflunomide), an approved medicine for relapsing forms of multiple sclerosis (MS), specifically targets highly metabolic and more autoreactive T-cells, analysis of the Phase 3 TERI-DYNAMIC clinical trial data shows. The findings, contrary to expectations, support a selective effect of Aubagio on different T-cell populations. The study “Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects” was published in the Science Translational Medicine journal. In MS, immune cells, or lymphocytes known as T-cells, attack and destroy myelin, the fat-rich substance that wraps around nerve fibers (axons). Myelin loss creates lesions that affect nerves of the brain and spinal cord. Previous evidence suggested that T-cells, depending on their active or resting state, rely on specific ways of energy production or metabolism. Aubagio, marketed by Sanofi Genzyme, is a well-known inhibitor of a mitochondrial enzyme called dihydroorotate dehydrogenase (DHODH), that is crucial for the activity of T-cells. However, how Aubagio selectively targets the autoreactive T-cells is poorly understood. To shed light on this matter, an international group of researchers used data from the TERI-DYNAMIC clinical trial that tested Aubagio in patients with relapsing form of MS to better understand how the therapy inhibited the patients' self-immune responses. The Phase 3, open-label TERI-DYNAMIC trial (NCT01863888) included 70 patients from Belgium, Germany, and The Netherlands, aged 18 to 56. Participants received Aubagio as a 14 milligram (mg) once-daily, oral dose, and researchers assessed the changes in immune cells' profile up to 24 weeks. Results showed that, contrary to what was expected, Aubagio was not generally decreasing T-cell levels in treated patients. Instead, it significantly reduced a particular subset of T-cells, called "Th1 helper cells." Moreover, researchers found that the diversity of T-cell receptors — the surface proteins that can recognize a particular antigen (a protein that can elicit an immune response) — making T-cells specific to a certain target was reduced in MS patients after treatment with Aubagio. These findings suggested that some T-cells were particularly susceptible to Aubagio. Using a mouse model for MS, the experimental autoimmune encephalomyelitis (EAE) model, researchers showed that the CD4+ T-cells (helper T-cells) and CD8+ T-cells, those that reacted most strongly against self-antigens, were the most sensitive to DHODH inhibition by Aubagio. Moreover, researchers saw that Aubagio was not affecting the production of pro-inflammatory molecules — called cytokines — at the cell level, but their overall decrease probably was due to the reduction in T-cell numbers. In line with these findings, CD4+ T-cells that produced the cytokine interferon gamma were significantly reduced with Aubagio treatment, whereas CD4+ T-cells that produced interleukin 17A were unchanged. This suggests that Aubagio is able to interfere with specific sub-types of immune cells. When the team compared the metabolic profile of T-cells from healthy subjects with that from patients with relapsing-remitting MS (RRMS) in both remission and in relapse phases, they found that the metabolism of T-cells from the last group was significantly altered, and thus targetable. Altogether, the results suggested that T-cells with a high-affinity to self-antigens are more susceptible to inhibition of the DHODH enzyme by Aubagio. “Therapeutic targeting of metabolic alterations might represent an attractive concept in MS, and might represent an as yet unrecognized key mechanism of teriflunomide-mediated immune modulation in this disease,” the researchers concluded.

Stress-induced changes in gut bacteria, or gut microbiota, may play a significant part in the possible link between exposure to stress and the risk of autoimmune disorders such as multiple sclerosis (MS), a mouse research study says. In the study “…

Early, positive safety results from a Phase 1 trial testing a potential immunotherapy, ATA188, in people with progressive multiple sclerosis will be detailed at the 5th Congress of the European Academy of Neurology (EAN) late next month, its developer, Atara Biotherapeutics, announced. ATA188 is an investigational and “off-the-shelf”…

Reactivation of ancient viruses incorporated into the human genome in the course of evolution may be involved in the acute inflammatory response that is characteristic of multiple sclerosis (MS), a study says. The findings of the study, “Expression of endogenous retroviruses reflects increased usage of atypical enhancers in…