{"id":12134,"date":"2017-01-19T00:00:54","date_gmt":"2017-01-19T08:00:54","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=12134"},"modified":"2024-01-30T15:33:16","modified_gmt":"2024-01-30T23:33:16","slug":"curb-immune-enthusiasm","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/curb-immune-enthusiasm\/","title":{"rendered":"Curb your immune enthusiasm"},"content":{"rendered":"<p>LA JOLLA\u2014Normally when we think of viruses, from the common cold to HIV, we want to boost people\u2019s immunity to fight them. But for scientists who develop therapeutic viruses (to, for example, target cancer cells or correct gene deficiencies) a more important question is: How do we keep people\u2019s natural immune responses at bay? In these cases, an overenthusiastic immune response actually undermines the therapy.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-10 col-md-push-1\"><div class=\"video-anchor\" id=\"video-5Gp_mLjX00k\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/5Gp_mLjX00k?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>Salk Institute researchers discovered that inhibiting a protein called phospholipid scramblase 1 (PLSCR1) controls the infected cell\u2019s antiviral response and provides long-term protection from immune attack and excessive inflammation. The results, described in the January 19, 2017, issue of <a href=\"http:\/\/www.cell.com\/neuron\/fulltext\/S0896-6273(16)30994-1\"><em>Neuron<\/em><\/a>, hold promise both for virally delivered treatments and inflammatory conditions like infections;\u00a0<a href=\"https:\/\/www.salk.edu\/de\/science\/research\/immune-system-biology\/\">autoimmune disorders<\/a> such as lupus; or <a href=\"https:\/\/www.salk.edu\/de\/science\/research\/neuroscience-and-neurological-disorders\/\">neurodegenerative diseases<\/a> such as Alzheimer\u2019s disease.<\/p>\n<figure id=\"attachment_12137\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"300\" class=\"img-responsive wp-image-12137 size-pr-300\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-300x300.jpg\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-300x300.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-150x150.jpg 150w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-768x768.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-1024x1024.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-767x767.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-147x147.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-458x458.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-585x585.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-553x553.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-750x750.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab-945x945.jpg 945w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-caption-text\">Salk Institute researchers discovered that inhibiting the protein PLSCR1 controls the infected cell\u2019s antiviral response and provides long-term protection from immune attack and excessive inflammation. In the cortex of a mouse, adenovirus-transduced cells (red) appear among labeled microglia (dark blue) and subsets of neurons (light blue) <\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/ResearchImage_NimmerjahnLab.jpg\" target=\"_blank\" rel=\"noopener\">Klicken Sie hier<\/a> for a high-resolution image<\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>\u201cNormally, the immune system will quickly recognize and act upon potential threats such as virally infected cells,\u201d says <a href=\"https:\/\/www.salk.edu\/de\/scientist\/axel-nimmerjahn\/\">Axel Nimmerjahn<\/a>, assistant professor in Salk\u2019s <a href=\"https:\/\/www.salk.edu\/de\/science\/research-centers\/waitt-advanced-biophotonics-center\/\">Waitt Advanced Biophotonics Center<\/a> and senior author of the new paper. \u201cBut in targeting PLSCR1, we\u2019ve effectively shielded infected cells from immune attack and increased gene expression from an engineered virus from a few days or weeks to at least six months, creating the potential for much longer-lasting therapies.\u201d<\/p>\n<p>Because viruses have evolved such effective methods for finding their target and utilizing the host cells\u2019 own molecular machinery, scientists are modifying viruses into long-lasting therapeutic vehicles that can deliver drugs to specific cells or tissues or selectively target and destroy tumors. But, since our immune systems don\u2019t discriminate between destructive and therapeutic viruses, researchers must devise ways to keep the immune system from destroying the helpful versions.<\/p>\n<p>To better understand the brain\u2019s immune response, the Salk team injected an engineered adenovirus (often used to deliver gene therapy) into mouse brains and monitored both the infected and immune cells\u2019 signaling and protein production in response to infection. Infected cells put out a variety of distress calls, including a molecular flag called phosphatidylserine that summons microglia, specialized immune cells in the brain. Microglia assess the situation and then decide whether to leave the infected cells alone or destroy them. Leaving the distressed cells alone risks having them cause collateral damage to other cells, while destroying them eliminates potentially critical brain cells, many of which don\u2019t regenerate. To better understand the calculus of this decision, the Salk team manipulated levels of the various proteins involved in the cell\u2019s intra- and extracellular communication, including PLSCR1.<\/p>\n<p>Surprisingly, ramping down PLSCR1 caused a wide variety of immune-related changes. Besides keeping microglia at bay, less PLSCR1 resulted in reduced production of inflammatory molecules called cytokines, whose typical role is to recruit more immune cells to the fight. \u201cWhen we saw how much inhibiting PLSCR1 reduced the inflammatory response, we immediately wondered if this mechanism could apply more broadly, not just to virus infection of the brain, but to other types of infections or even autoimmune diseases,\u201d says Yusuf Tufail, a former Salk postdoctoral fellow and first author of the paper.<\/p>\n<figure id=\"attachment_12138\"  class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"250\" class=\"img-responsive wp-image-12138 size-pr-300\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-300x250.jpg\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-300x250.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-768x641.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-1024x854.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-147x123.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-458x382.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-585x488.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-553x461.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-750x626.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5-945x788.jpg 945w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-caption-text\">Yusuf Tufail (front) and Axel Nimmerjahn<\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/Yusuf-Tufail_Axel-Nimmerjahn_IMG_7656-5.jpg\" target=\"_blank\" rel=\"noopener\">Klicken Sie hier<\/a> for a high-resolution image<\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>The protective effects of inhibiting PLSCR1 lasted for all time points investigated (up to six months); none of the other manipulated proteins had such a pronounced result. Because PLSCR1 is present throughout the body, not just in the brain, researchers plan to investigate the role of PLSCR1 in other inflammatory conditions.<\/p>\n<p>\u201cGiven how complex the immune response is, and how many genes are regulated up or down in response to infection, it was amazing to find a single protein that controls so many pathways,\u201d says Nimmerjahn. \u201cImagine a small molecule inhibitor that a patient could take to curb excessive inflammation. This could have a hugely beneficial effect on many disease outcomes.\u201d<\/p>\n<p>Other authors included: Daniela Cook, Lawrence Fourgeaud, Colin J. Powers, Katharina Merten, Charles L. Clark, Elizabeth Hoffman, Alexander Ngo, Kohei J. Sekiguchi, <a href=\"https:\/\/www.salk.edu\/de\/scientist\/clodagh-oshea\/\">Clodagh C. O\u2019Shea<\/a>, and <a href=\"https:\/\/www.salk.edu\/de\/scientist\/greg-lemke\/\">Greg Lemke<\/a> of Salk.<\/p>\n<p>The work was funded by grants from the <a href=\"https:\/\/www.nih.gov\/\" target=\"_blank\" rel=\"noopener\">Nationale Gesundheitsinstitute<\/a>; the <a href=\"http:\/\/ritaallen.org\/\" target=\"_blank\" rel=\"noopener\">Rita Allen<\/a>, <a href=\"http:\/\/www.whitehall.org\/\" target=\"_blank\" rel=\"noopener\">Whitehall<\/a>, <a href=\"https:\/\/thebrf.org\/\" target=\"_blank\" rel=\"noopener\">Brain Research<\/a>, <a href=\"http:\/\/waittfoundation.org\/\" target=\"_blank\" rel=\"noopener\">Waitt<\/a>, <a href=\"http:\/\/www.hearstfdn.org\/\" target=\"_blank\" rel=\"noopener\">Hearst<\/a>, and Richard Allan Barry Family foundations; the <a href=\"http:\/\/www.helmsleytrust.org\/\" target=\"_blank\" rel=\"noopener\">Die gemeinn\u00fctzige Stiftung von Leona M. und Harry B. Helmsley<\/a>; the <a href=\"http:\/\/nomisfoundation.ch\/\" target=\"_blank\" rel=\"noopener\">Nomis<\/a>, <a href=\"http:\/\/hnberger.org\/\" target=\"_blank\" rel=\"noopener\">H. N. and Frances C. Berger<\/a>, Fritz B. Burns, and HKT foundations; Frederik Paulsen and Franc\u0327oise Gilot-Salk; the <a href=\"https:\/\/www.cancer.gov\/\" target=\"_blank\" rel=\"noopener\">National Cancer Institute<\/a>; the William Scandling Trust; the <a href=\"http:\/\/pricephilanthropies.org\/\" target=\"_blank\" rel=\"noopener\">Price Family Foundation<\/a>; the Marshall Legacy Foundation; a <a href=\"http:\/\/www.lsrf.org\/\" target=\"_blank\" rel=\"noopener\">Life Sciences Research Foundation<\/a> and Pioneer Fund postdoctoral scholar award; and a <a href=\"http:\/\/www.dfg.de\/en\/\" target=\"_blank\" rel=\"noopener\">Deutsche Forschungsgemeinschaft<\/a> (DFG) and Catharina Foundation postdoctoral scholar award.<\/p>","protected":false},"featured_media":12135,"template":"","faculty":[89],"disease-research":[459,122],"class_list":["post-12134","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-axel-nimmerjahn","disease-research-glial-biology","disease-research-immune-system-biology"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Curb your immune enthusiasm - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/de\/news-release\/curb-immune-enthusiasm\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Curb your immune enthusiasm - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Normally when we think of viruses, from the common cold to HIV, we want to boost people\u2019s immunity to fight them. 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