regulatory T-cells

The protein DDX39B is a master regulator of immune tolerance, or the immune system’s ability to distinguish self from potentially harmful nonself molecules, and helps to control the development of immune cells that are key for this process, a new study shows. Findings suggest that activating DDX39B with small molecules…

A Phase 1/2 clinical trial is evaluating the safety and effectiveness of a cutting-edge immunotherapy called extracorporeal photopheresis in people with multiple sclerosis (MS). The study, dubbed PHOMS (NCT05168384), is enrolling up to 45 adults with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) at a…

Six months of treatment with foralumab, an experimental nasal spray, safely and effectively improved motor and cognitive function while easing immune activation and inflammatory responses in a person with secondary progressive multiple sclerosis (SPMS), Tiziana Life Sciences, the therapy’s developer, announced. The patient — the first with MS to…

Treatment with an autologous hematopoietic stem cell transplant (aHSCT) seems to reboot the immune system in multiple sclerosis (MS) patients for at least three years, a small study found. The study, “Sustained immunotolerance in multiple sclerosis after stem cell transplant,” was published in Annals of Clinical and…

Sonoma Biotherapeutics has raised $265 million in investment funding to support the development and production of novel immune T-cell therapies to treat severe autoimmune and inflammatory diseases, such as multiple sclerosis (MS). “We are ushering in a new era of medicine, using immune cells as living therapies that…

Removing an ion channel called Piezo1 from immune T-cells lessened disease severity in a mouse model of multiple sclerosis (MS), a study showed. Notably, these beneficial effects were associated with an expansion of regulatory T-cells (Tregs) — a type of immune cell that typically dampens immune and inflammatory responses —…

Editor’s note: The Multiple Sclerosis News Today news team is providing in-depth and unparalleled coverage of the virtual ACTRIMS Forum 2021, Feb. 25–27. Go here to see the latest stories from the conference. Regulatory immune cells expressing the melanoma cell adhesion molecule (MCAM) dampen inflammation at sites of nerve damage in…

Regulatory T-cells (Tregs) — immune cells that normally dampen immune and inflammatory responses by inhibiting the activity of pro-inflammatory immune cells — enabled mice in a model of multiple sclerosis to partly recover from limb and tail paralysis, scientists reported. Tregs can do this by preventing a subtype of…

A short-chain fatty acid produced by gut bacteria helps to counteract inflammatory responses in multiple sclerosis (MS) by promoting greater numbers of regulatory immune cells, a study reports. But the bacterial composition of the gut (its microbiome) of MS patients is deficient in bacteria that produce this acid —…

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…

Exosomes — tiny vesicles secreted by cells — collected from bone marrow stem cells and injected into a mouse model of multiple sclerosis (MS) helped to treat the disease, a study reports. Specifically, this treatment eased myelin loss and neuroinflammation in the mice, and improved motor function, the…

A tiny molecule known as microRNA-142 plays a key role in the prevention of autoimmune responses through immune cells called regulatory T-cells (Tregs), according to a new study of  mice. These findings could enable new strategies to treat multiple sclerosis (MS) and other autoimmune diseases, the scientists said. The…

Treating a common animal model of multiple sclerosis (MS) with a typhoid vaccine eased disease symptoms by prompting T helper cells to stop production of a pro-inflammatory factor — interleukin (IL)-17 — and by promoting greater numbers of anti-inflammatory  regulatory T-cells, researchers report. Their study, “Targeting prohibitins at the…

Propionic acid supplements alter the composition and behavior of immune cells in multiple sclerosis (MS) patients — likely by changing the composition of gut bacteria, according to Alexander Duscha from Ruhr University Bochum in Bochum, Germany. The finding, presented Wednesday at the 7th Joint ECTRIMS-ACTRIMS Meeting running in Paris…

The discovery of an immune cell quality control mission may have put scientists a step closer to understanding how autoimmune conditions such as multiple sclerosis arise. University of Alabama at Birmingham researchers identified regulatory immune cells with the quality control mission of destroying antibody-producing B-cells that mistakenly target the body's own tissue after an infection. An autoimmune disease is one in which the immune system attacks healthy tissue or organs instead of invaders. Eventually, the insight could lead researchers to new approaches for treating MS and other conditions caused by aberrant immune reactions. The Alabama researchers were studying the processes involved in the body's defense against a real threat — the influenza virus — when they discovered a population of immune cells whose action is relevant to autoimmune diseases. The study noted that T follicular regulatory cells appeared in the late stages of influenza infection. Their objective was to prevent the immune system from generating self-reactive antibodies — that is, those that attack the body's own tissue. These cells are poorly understood, the researchers explained. Their experiments, published in the journal Nature Immunology, focused on the molecular events surrounding the cells’ actions.  The team discovered that about a week after the infection, levels of an immune regulator called the IL-2 protein increased. This triggered the multiplication of common regulatory T-cells, or Tregs. When this phase of the immune reaction was fading, TFR cells started multiplying, reaching peak numbers about a month after infection. The formation of the TFR cells was therefore tightly linked to the processes controlling Treg production, researchers said, with falling levels of IL-2 allowing the new phase of the immune response. The TFR cells migrated to the lymph nodes — the headquarters of antibody-producing B-cells. Here, B-cells proliferate and change their antibody-producing genes to create new, stronger antibodies. But sometimes the gene changes, or mutations, give rise to an antibody that attacks the body, instead of invaders. Researchers discovered that TFR cells prevented B-cells, which gave rise to autoantibodies, from accumulating in the lymph nodes. Importantly, the TFR cells had no impact on the immune processes targeting the influenza virus. When researchers prevented TFR cells from forming or removed them from mice, the animals started producing autoantibodies, they explained. While this suggested that people with autoimmune diseases may have flawed TFR processes, the study did not investigate this, making the topic a possibility for future studies.

Researchers have taken the first steps towards the development of a gene therapy for multiple sclerosis — a treatment that boosted anti-inflammatory immune processes and reversed severe paralysis in mouse models of the disease. The University of Florida Health research team said it was optimistic that the therapy can work…

Eli Lilly and Nektar Therapeutics have established a development and commercial agreement for the investigational T-cell stimulator therapy NKTR-358 for the treatment of autoimmune disorders, including multiple sclerosis. NKTR-358, discovered and initially developed by Nektar, has the potential to modulate immune system responses to re-establish an immune balance in patients with autoimmune disorders. The treatment targets the interleukin 2 receptor complex (IL-2R) that is expressed on the surface of a subset of immune cells called regulatory T-cells, or Tregs. NKTR-358 activity stimulates the proliferation of Tregs, which in turn will regulate the activity of other immune cells that are uncontrolled and are responsible for the underlying mechanisms of autoimmune disorders. "We look forward to working with Nektar to study this novel approach to treating a number of autoimmune conditions," Thomas F. Bumol, PhD, senior vice president of biotechnology and immunology research at Eli Lilly, said in a press release. "NKTR-358 is an exciting addition to our immunology portfolio and reinforces Lilly's commitment to sustain a flow of innovative medicines in our pipeline." Bumol added. Under the agreement, Lilly and Nektar will continue to jointly develop NKTR-358. Nektar will be responsible for completing the ongoing Phase 1 clinical study; and Phase 2 clinical development costs will be shared by the two companies, with Lilly covering 75 percent of the costs and Nektar the remaining 25 percent. Nektar will have the option to take part of the Phase 3 development of NKTR-358 on an indication-by-indication basis. "We are very pleased to enter into this collaboration with Lilly as they have strong expertise in immunology and a successful track record in bringing novel therapies to market," said Howard W. Robin, president and CEO of Nektar. "Importantly, this agreement enables the broad development of NKTR-358 in multiple autoimmune conditions in order to achieve its full potential as a first-in-class resolution therapeutic." Based on the announced agreement, Lilly will pay an initial amount of $150 million to Nektar, which will also be eligible to receive up to $250 million from additional development and regulatory milestones. In the future, Nektar may also receive royalties from the product depending on its investment in NKTR-358’s Phase 3 development and future product sales. Lilly will cover all costs of global marketing of NKTR-358, and Nektar will have an option to co-promote the drug in the United States.

A gene mutation may explain the uncontrolled, inflammatory immune response seen in autoimmune and chronic inflammatory diseases like multiple sclerosis, scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) report. It's a discovery that, they said, appears to be "a big step in the right direction." According to the study, published in the journal Science Immunology, alterations in the FOXP3 gene affect specific immune cells called regulatory T-cells, or Tregs. Those mutations hamper Tregs in performing a crucial regulatory role, leading to a loss of control over the immune system’s response to a perceived threat. “We discovered that this mutation in the FOXP3 gene affects the Treg cell’s ability to dampen the immune response, which results in the immune system overreacting and causing inflammation,” Ciriaco Piccirillo, the study's lead author and an immunologist in the Infectious Diseases and Immunity, Global Health Program, at the RI-MUHC, said in a news release. Tregs are known to be the immune system players responsible for keeping other immune cells under control, preventing them from attacking the host’s own tissues, while maintaining a proper immune response against harmful agents. The normal activity of Treg cells is essential for preventing excessive immune reactions. The FOXP3 gene is also well-known, and documented, to be essential for proper Treg cell function. However, the mechanisms by which FOXP3 gene is involved in Treg cell activities are still poorly understood. In the study, “Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions,” the research team — in collaboration with researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan — evaluated the impact of a FOXP3 gene mutation in autoimmunity response. Taking advantage of cutting-edge technology, the team studied samples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. Interestingly, the researchers found that this genetic variant did not reduce the number of Treg cells or the levels of FOXP3 protein. Instead, the mutation altered the way Tregs could suppress other immune cells to prevent overactivation. “What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response,” said Piccirillo. “Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions,” added Khalid Bin Dhuban, the study's first author and a postdoctoral fellow in Piccirillo’s laboratory. The team developed a compound capable of restoring Treg cells' ability to control the immune system in the presence of this specific FOXP3 gene mutation. Tested in animal models of colitis and arthritis, two chronic inflammatory diseases, the compound reduced inflammation and restored normal Treg function. Researchers now plan to develop similar drugs that may be of use in other diseases where Treg cells are known to be defective, including multiple sclerosis, type 1 diabetes, and lupus. "Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," said Piccirillo. “Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer.” “This discovery gives us key insights on how Treg cells are born and how they can be regulated,” Piccirillo added. “With this discovery, we are taking a big step in the right direction.”

Researchers managed to change the immune system — replacing inflammation with immune tolerance — in a mouse model of multiple sclerosis (MS) using so-called quantum dots, or nano-sized particles carrying pieces of myelin. Experiments with this advanced technological solution may help researchers design MS therapies that are based on promoting regulatory T-cells rather…

Nektar Therapeutics has started a Phase 1 clinical trial of its biologic therapy NKTR-358 for inflammatory disorders and autoimmune diseases like multiple sclerosis. NKTR-358 is a first-in-class regulatory T-cell stimulator designed to correct the immune system dysfunction associated with these disorders. It targets regulatory T-cells, or Tregs. Other immunosuppressant therapies suppress the…

CGEN-15001, which could become the first tolerance-inducing therapy for multiple sclerosis (MS) and other autoimmune conditions, is on the agenda of a scientific conference in Canada that is going on now and another conference in May. The first CGEN-15001 presentation that Compugen is delivering is at the Keystone Symposia: Immune Regulation in Autoimmunity and…

Regulatory T-cells in the central nervous system trigger the maturation of stem cells that increase the production of myelin at injured neurons — a discovery that places the idea of regeneration in multiple sclerosis (MS) in a whole new light. Myelin is a substance essential to the functioning of the…

Three researchers who discovered regulatory T-cells and their role in autoimmune diseases, such as multiple sclerosis (MS), have been awarded the Crafoord Prize by The Royal Swedish Academy of Sciences. The scientists — Shimon Sakaguchi, Fred Ramsdell, and Alexander Rudensky — are credited with advancing understanding of how the body…

Immunization with molecules present specifically in myelin may be a new approach to treating multiple sclerosis (MS), according to a recent study that found that the mouse version of such molecules could stop ongoing disease processes in an MS mouse model. The study, “Targeting Non-classical Myelin Epitopes to Treat…

Researchers at the University of Heidelberg, Germany, recently showed that peripheral blood cells loaded with a drug that resembles the myelin protein are able to inhibit harmful immune responses and prevent relapses in a mouse model of relapsing-remitting multiple sclerosis (MS). The findings were described in the study “…

Natalizumab (Tysabri) harnesses multiple sclerosis (MS) activity by targeting CD49, a molecule on the surface of immune cells. Now, researchers found that the drug reduces the factor on regulatory T-cells to a greater extent than on inflammatory T-cells — a mechanism that might explain disease exacerbation during treatment. The molecule under…