August 23, 2017 News by Alice Melão, MSc

Researchers Identify Nerve Pathway Linking Brain Inflammation, Gut Dysfunction in MS

Chronic stress and inflammation in the brain can cause multi-organ dysfunction including severe gut failure, mediated by a newly identified nerve pathway in animal models of multiple sclerosis, a Japanese study shows. MS is an autoimmune disease caused by CD4+ T-cells that cross the blood-brain barrier protecting the central nervous system. This inflames and stresses the brain and spinal cord. In previous studies, a team led by professor Masaaki Murakami of Japan's Hokkaido University showed that these cells could cross the blood-brain barrier in specific sites. These entrance sites depend on brain regional activation, which was found to be triggered by specific nerve interactions — a mechanism the team called gateway reflexes. In collaboration with other Japanese researchers and a team from Germany, the project aimed to address the potential correlation among chronic stress, brain inflammation and organ failures in MS. Using mice with MS-like disease — the experimental autoimmune encephalomyelitis model — researchers found that animals that had autoreactive CD4+ T-cells and which were exposed to stressful conditions developed severe symptoms such as gastrointestinal failure, or even death. Detailed analysis of the animals' brains showed that in stressed mice, CD4+ T-cells accumulated in two specific sites in the center of the brain around blood vessels. This event would cause inflammation around those vessels, and activation of a nerve pathway that is commonly turned off. This switch led to gut dysfunction, bleeding and failure. "These results demonstrate a direct link between brain micro-inflammation and fatal gastrointestinal diseases via the establishment of a new neural pathway under stress," Murakami, the study's senior author, said in a news release. Researchers were able to prevent gut symptoms by inhibiting inflammation in the brain or blocking the nerve pathway responsible for driving the signals from the brain to the gastrointestinal tract. "Micro-inflammation in the brain is also seen in Alzheimer's disease and Parkinson's disease," Murakamai concluded. "So it's of particular interest to investigate possible connections between brain micro-inflammations and organ dysfunctions, including those within the brain itself, in those patients."

August 16, 2017 News by Iqra Mumal, MSc

Enzyme Regulates Development of Specific T-cells That Contribute to Autoimmune Disease, Study Suggests

A new study highlights a crucial role for the enzyme protein tyrosine phosphatase N2 in the development of early immune T-cells, and suggests that decreased levels of this enzyme can lead to the production of subsets of T-cells that contribute to the development of autoimmune diseases such as multiple sclerosis. T-cells, which are a type of immune cells that fight infection, are composed of multiple subsets that have different roles in immunity. Researchers at Monash University set out to characterize the role of PTPN2 in early T-cell development and in the development of T-cell subsets αβ TCR and γδ TCR. To do this, researchers deleted the gene coding for PTPN2 and looked at the resulting T-cell population. Results demonstrated that the deletion of PTPN2 led to the production of γδ T-cells with pro-inflammatory properties that have been associated with many autoimmune diseases by inhibiting certain pathways that regulate proper T-cell development. “This is an important advance in our understanding of critical checkpoints in T-cell development,” Tony Tiganis, principal research fellow in the Department of Biochemistry and Molecular Biology at Monash University in Australia, said in a press release. “It helps decide whether the progenitors go on to become T-cells or something else; if they become one type of T-cell or another type.” Interestingly, there are already drugs that target some of the pathways that PTPN2 regulates, which could lead to the use of existing drugs to treat some of these autoimmune diseases, including MS. “Understanding the mechanisms that govern early T-cell development and how these are altered in human disease may ultimately afford opportunities for novel treatments. This is very exciting,” said Florian Wiede, a post-doctoral candidate at Monash and first author of the study.

June 14, 2017 News by Patricia Inacio, PhD

Stressful Environment Triggers Inflammatory Cells Linked to Autoimmune Diseases Like MS, Study Shows

A stressful microenvironment, characterized by low metabolites and low oxygen levels, triggers the generation of immune cells directly implicated in a variety of inflammatory diseases, such as multiple sclerosis (MS). The study, “Cellular Stress in the Context of an Inflammatory Environment Supports TGF-β-Independent T Helper-17 Differentiation,” was…

May 4, 2017 News by Patricia Inacio, PhD

Cytomegalovirus Infection Worsens Multiple Sclerosis, Study in Mice Shows

A cytomegalovirus infection triggers an increase in inflammatory and cytotoxic immune cells in mice with multiple sclerosis (MS), which leads to enhanced inflammation and loss of nerve-protecting myelin. The study, “Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation,” was published in the journal Scientific Reports. A cytomegalovirus (CMV) infection…

April 5, 2017 News by Joana Fernandes, PhD

UCSF Neurologist Played Key Role in MS Research Turning to B-Cells, Essential Step to Ocrevus

Dr. Stephen Hauser, chair of the neurology department at the University of California San Francisco, was instrumental in the early research and later clinical trials that ultimately led to Ocrevus (ocrelizumab), the first therapy approved by the U.S. Food and Drug Administration (FDA) for both relapsing MS (RMS) and primary progressive multiple sclerosis…

February 24, 2017 News by Patricia Silva, PhD

#ACTRIMS2017 – Some Fatty Acids in Diet Help, Others Hurt Immune System, Study Reports

Short-chain dietary fatty acids, such as propionate, drive the production of regulatory immune T-cells in patients with multiple sclerosis (MS), while long-chain acids promote T-cells that are involved in inflammatory processes. Since the beneficial fatty acids are safe and can be obtained as over-the-counter dietary supplements, researchers suggest they could…

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