Nicholas Weiler / en Treating brain inflammation in MS patients may start in their guts: 老司机直播-led study /news/treating-brain-inflammation-ms-patients-may-start-their-guts-u-t-led-study <span class="field field--name-title field--type-string field--label-hidden">Treating brain inflammation in MS patients may start in their guts: 老司机直播-led study</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/Jen-Gommerman-and-Olga-Rojas%2C-by-Jim-Oldfield-%28web-lead%29.jpg?h=afdc3185&amp;itok=jgUCZ5Ct 370w, /sites/default/files/styles/news_banner_740/public/Jen-Gommerman-and-Olga-Rojas%2C-by-Jim-Oldfield-%28web-lead%29.jpg?h=afdc3185&amp;itok=9wZb_76P 740w, /sites/default/files/styles/news_banner_1110/public/Jen-Gommerman-and-Olga-Rojas%2C-by-Jim-Oldfield-%28web-lead%29.jpg?h=afdc3185&amp;itok=6igR2DdF 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/Jen-Gommerman-and-Olga-Rojas%2C-by-Jim-Oldfield-%28web-lead%29.jpg?h=afdc3185&amp;itok=jgUCZ5Ct" alt="photo of Jen Gommerman and Olga Rojas"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2019-01-07T09:45:49-05:00" title="Monday, January 7, 2019 - 09:45" class="datetime">Mon, 01/07/2019 - 09:45</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">老司机直播 Professor Jen Gommerman (left), the study's senior author, says the research highlights the importance of the 鈥済ut-brain axis鈥 in MS patients. She is pictured here with 老司机直播 postdoctoral researcher and co-author Olga Rojas (photo by Jim Oldfield)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/jim-oldfield" hreflang="en">Jim Oldfield</a></div> <div class="field__item"><a href="/news/authors-reporters/nicholas-weiler" hreflang="en">Nicholas Weiler</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/global-lens" hreflang="en">Global Lens</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/faculty-medicine" hreflang="en">Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/immunology" hreflang="en">Immunology</a></div> <div class="field__item"><a href="/news/tags/research-and-innovation" hreflang="en">Research and Innovation</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers at the University of Toronto and University of California, San Francisco have discovered that the intestine is the source of immune cells that reduce brain inflammation in people with multiple sclerosis, and that increasing the number of these cells blocks inflammation entirely in a preclinical model of the disease.</p> <p>The cells in question are plasma cells 鈥 white blood cells that originate as B cells in bone marrow but change their behavior when triggered by microbes in the gut. Studying mice and samples from human MS patients, the researchers found that plasma cells that reside in the gut and produce Immunoglobulin A (IgA) antibodies appear to migrate to the central nervous system and produce an anti-inflammatory effect during MS flare-ups.</p> <p>MS is an autoimmune disease, driven by other types of immune cells (including B and T cells) that attack myelin, the protective coating that surrounds nerve fibers. Recent clinical studies have shown drugs that target B cells mitigate MS, while those that target plasma cells make the disease worse. The current study offers an explanation for these divergent results.</p> <p>鈥淲e already knew what was and was not working in the clinic,鈥 says <strong>Jen Gommerman</strong>, a professor of immunology at 老司机直播 and the study's senior author. 鈥淏ut here we鈥檝e uncovered the molecular and cellular mechanism at play. It鈥檚 a kind of reverse translation approach, which highlights the importance of the gut-brain axis in MS and other autoimmune conditions.鈥</p> <p>The results were published online Jan. 3&nbsp;<a href="https://www.cell.com/cell/fulltext/S0092-8674(18)31560-5">in the journal <em>Cell</em></a>.</p> <p>Canada and the United States have among the highest rates of MS in the world, with around three in every thousand individuals affected. Symptoms can include fatigue, poor coordination, tingling, organ problems and cognitive impairment. There is no cure, although quicker diagnoses and better drugs have improved outcomes significantly in the last 15 years.&nbsp;</p> <p>鈥淚gAs comprise 80 per cent of all antibodies in the body, yet their exact function is still not fully understood,鈥 says Sergio Baranzini, a co-author on the paper who is a professor of neurology in the UCSF Weill Institute for Neurosciences. 鈥淪howing that IgA-producing B cells can travel from the gut to the brain opens a new page in the book of neuroinflammatory diseases and could be the first step towards producing novel treatments to modulate or stop MS and related neurological disorders.鈥</p> <p>The lead authors on the work are 老司机直播 postdoctoral fellows <strong>Olga Rojas</strong>&nbsp;and <strong>Elisa Porfilio</strong>,<strong>&nbsp;</strong>from Gommerman's lab, and Anne-Katrin Pr枚bstel, from Baranzini's lab at UCSF. In a moment of scientific serendipity, they recently presented their research at the same conference and realized their results aligned. The researchers began to collaborate, and Pr枚bstel and colleagues in the Baranzini lab were able to show that the Gommerman lab鈥檚 findings in mice had parallels to human MS patients.&nbsp;</p> <p>Specifically, the UCSF team found evidence that IgA decreased in fecal samples from patients with active MS neuroinflammation, suggesting that the inflammation-suppressing cells had been recruited to help fight the patients鈥 disease.</p> <p>One promising aspect of the new research is that increasing the number of IgA plasma cells that migrate from the gut to the brain eradicated neuroinflammation in mice. A therapeutic approach might aim to expand the number of these cells in the gut, enabling a plentiful supply that could move to the brain and dampen inflammation.&nbsp;</p> <p>鈥淎s a clinician-scientist, it is exciting that our experiments linking preclinical animal models to the biology we see in real MS patients may have uncovered a general mechanism for how the immune system counteracts inflammation,鈥 says UCSF鈥檚 Pr枚bstel. 鈥淯ntil now, no one has really studied these IgA-producing plasma cells in the context of disease, but we are now examining them in detail in patients with MS to begin to understand how we might manipulate them to help treat neuroinflammatory disease.鈥</p> <p>A key next step for the researchers is to figure out what microbes in the gut promote the generation of immunosuppressive IgA plasma cells. 鈥淚f we can understand what these cells are reacting to, we can potentially treat MS by modulating our gut commensals,鈥 says Gommerman, referring to the bacteria that live in the healthy gut. 鈥淭hat might be easier than getting drugs into the brain, which is a strategy that hasn鈥檛 always worked in MS.鈥</p> <p>The study also raises questions about the microbiome and lifestyle choices. Do certain lifestyles nudge some people toward a gut microbiome that allows immunosuppressive plasma cells to flourish? Are specific foods conducive to creating that environment and, if so, might a drug or supplement mimic the effect? Genetics are just one factor that affect susceptibility to MS; the current study highlights how non-genetic factors may confer disease resistance.</p> <p>Gommerman plans to pursue the basic science behind these questions, working with Baranzini and other research groups to bring the findings into the clinical realm. 鈥淭here is something very critical about how the gut and brain are connected, and we鈥檙e starting to unravel the molecular threads behind that clinical observation,鈥 she says. 鈥淚t鈥檚 a great example of how fast science can move.鈥</p> <p>The research was supported by the Canadian Institutes of Health Research, the Canada Research Chairs Program and the&nbsp;Multiple Sclerosis Society of Canada's research foundation, among others.</p> <p><em>Nicholas Weiler is a public relations officer with the University of California, San Francisco</em></p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Mon, 07 Jan 2019 14:45:49 +0000 Christopher.Sorensen 150533 at