{"id":15316,"date":"2017-11-06T12:43:26","date_gmt":"2017-11-06T20:43:26","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=15316"},"modified":"2020-06-15T11:33:25","modified_gmt":"2020-06-15T18:33:25","slug":"immune-cell-policing-offers-insights-cancer-autoimmune-disease","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/","title":{"rendered":"Immune cell policing offers insights into cancer, autoimmune disease"},"content":{"rendered":"

LA JOLLA\u2014Regulatory T cells (Tregs) are the traffic cops of the immune system. They instruct other types of immune cells on when to stop and when to go. Learning how to direct the activity of Tregs has important implications for improving cancer immunotherapy as well as developing better treatments for autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.<\/p>\n

\"From
From left: Ruth Yu, Ye Zheng, Annette Atkins, Ronald Evans, Nanhai He, Michael Downes, Weiwei Fan, Brian Henriquez.<\/p>\n

Click here<\/a> for a high-resolution image<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

Now, a research team from the Salk Institute has uncovered for the first time a protein that controls both the survival and function of Tregs. The discovery, published in the Proceedings of the National Academy of Sciences<\/em> the week of November 6, 2017, suggests ways to influence the function of Tregs and ultimately to make immune-related therapies more effective.<\/p>\n

\u201cTregs are at the crossroads of inflammation,” says senior author \u7f57\u7eb3\u5fb7\u00b7\u57c3\u6587\u65af<\/a>, Howard Hughes Medical Institute investigator and holder of Salk\u2019s March of Dimes Chair in Molecular and Developmental Biology. \u201cIf you have a lot of Tregs in the environment, they weaken your immune response. If you have too few you go down the road of chronic inflammation.\u201d<\/p>\n

\u201cRight now there are no good targets for controlling Tregs,\u201d says Nanhai He, a research associate in Evans\u2019 laboratory and the study\u2019s first author. \u201cThis finding is very new and very important, because it shows us the role of cellular metabolism in how these immune cells function.\u201d<\/p>\n

The protein the team studied is called Lkb1 (for liver kinase B1). Kinases are enzymes that catalyze reactions inside cells. Lkb1 was previously known to play a role in cell metabolism, but until this study, investigators didn\u2019t know that it controls the functions in the immune response of Tregs.<\/p>\n

\u201cWhen we talk about metabolism, most people think about factors like what we eat and how much we exercise,\u201d says Annette Atkins, a staff researcher in Evans\u2019 lab. \u201cBut in this case, we\u2019re looking at the metabolism of individual cells. By compromising the ability of these cells to make energy, we see very profound autoimmune disorders.\u201d<\/p>\n

In the current study, the team used mouse models that had the Lkb1<\/em> gene knocked out in their regulatory T cells. The mice showed many symptoms of autoimmune disease and died within a few weeks of birth. Further examination revealed that the normal metabolic machinery in the Tregs was disrupted. The cells had defective mitochondria\u2014cellular power stations\u2014and depleted levels of ATP, which is their most important fuel source.<\/p>\n

\u201cThrough these observations, we determined that the Lkb1 pathway is responsible for supplying Tregs with energy,\u201d says Ye Zheng<\/a>, an associate professor in Salk\u2019s Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis. \u201cWithout it, Tregs don\u2019t have enough fuel to function.\u201d<\/p>\n

\"Skin
Skin samples from mice whose regulatory immune cells (Tregs) lack the Lkb1 protein (bottom) are under attack from other immune cells (purple dots) compared to normal mice whose Tregs have the Lkb1 protein (top).<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cIt turns out that Tregs require a lot of energy to do their job, which is essentially to prevent other kinds of T cells from attacking the body,\u201d adds Michael Downes, a Salk senior scientist. \u201cThis is something that wasn\u2019t previously recognized, and it\u2019s an important discovery.\u201d<\/p>\n

The investigators say the findings have implications for both cancer immunotherapy and therapy for autoimmune diseases.<\/p>\n

In cancer, Tregs are recruited by tumors and prevent other types of T cells, including cytotoxic T cells (also called CD8 cells) from attacking and destroying cancer cells. \u201cTo boost cancer immunotherapy, we\u2019d like to find ways to block the Lkb1 pathway,\u201d Zheng explains. \u201cThe outcome of this inhibition would be an increased immune response from other types of T cells, which would help them to destroy tumors.\u201d<\/p>\n

On the other hand, boosting the ability of Tregs to suppress other types of immune cells could prevent autoimmunity, by preventing these cells from attacking organs and other tissues. Boosting the Treg population also has potential to avert immune rejection after an organ transplant.<\/p>\n

The investigators say that although Lkb1 itself is difficult to target, they have already identified molecules downstream in the signaling pathway that could be altered with drugs. \u201cThese drugs could either inhibit or enhance the pathway, depending on what we want them to do,\u201d He explains. Further research from the team will focus on the development of such drugs.<\/p>\n

Other researchers involved in the study were Weiwei Fan, Brian Henriquez and Ruth Yu of Salk; and Christopher Liddle of the University of Sydney.<\/p>\n

This work was funded by the National Institutes of Health<\/a>, the National Institute of Environmental Health Sciences<\/a>, the Leona M. and Harry B. Helmsley Charitable Trust<\/a>, the Foundation Leducq<\/a> and Ipsen\/Biomeasure.<\/p>","protected":false},"featured_media":15377,"template":"","faculty":[91,56],"disease-research":[366],"class_list":["post-15316","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-ronald-evans","faculty-ye-zheng","disease-research-infectious-disease"],"acf":[],"yoast_head":"\nImmune cell policing offers insights into cancer, autoimmune disease - 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\/zh\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Immune cell policing offers insights into cancer, autoimmune disease - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Regulatory T cells (Tregs) are the traffic cops of the immune system. They instruct other types of immune cells on when to stop and when to go. Learning how to direct the activity of Tregs has important implications for improving cancer immunotherapy as well as developing better treatments for autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/zh\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"article:modified_time\" content=\"2020-06-15T18:33:25+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/11\/lpk1a.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"222\" \/>\n\t<meta property=\"og:image:height\" content=\"189\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\\\/\",\"name\":\"Immune cell policing offers insights into cancer, autoimmune disease - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2017\\\/11\\\/lpk1a.jpg\",\"datePublished\":\"2017-11-06T20:43:26+00:00\",\"dateModified\":\"2020-06-15T18:33:25+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\\\/#breadcrumb\"},\"inLanguage\":\"zh-CN\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"zh-CN\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2017\\\/11\\\/lpk1a.jpg\",\"contentUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2017\\\/11\\\/lpk1a.jpg\",\"width\":222,\"height\":189},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Immune cell policing offers insights into cancer, autoimmune disease\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"zh-CN\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"zh-CN\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Immune cell policing offers insights into cancer, autoimmune disease - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/zh\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/","og_locale":"zh_CN","og_type":"article","og_title":"Immune cell policing offers insights into cancer, autoimmune disease - Salk Institute for Biological Studies","og_description":"LA JOLLA\u2014Regulatory T cells (Tregs) are the traffic cops of the immune system. They instruct other types of immune cells on when to stop and when to go. Learning how to direct the activity of Tregs has important implications for improving cancer immunotherapy as well as developing better treatments for autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.","og_url":"https:\/\/www.salk.edu\/zh\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/","og_site_name":"Salk Institute for Biological Studies","article_modified_time":"2020-06-15T18:33:25+00:00","og_image":[{"width":222,"height":189,"url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/11\/lpk1a.jpg","type":"image\/jpeg"}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"4 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/","url":"https:\/\/www.salk.edu\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/","name":"Immune cell policing offers insights into cancer, autoimmune disease - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.salk.edu\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/#primaryimage"},"image":{"@id":"https:\/\/www.salk.edu\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/#primaryimage"},"thumbnailUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/11\/lpk1a.jpg","datePublished":"2017-11-06T20:43:26+00:00","dateModified":"2020-06-15T18:33:25+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/#breadcrumb"},"inLanguage":"zh-CN","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/"]}]},{"@type":"ImageObject","inLanguage":"zh-CN","@id":"https:\/\/www.salk.edu\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/#primaryimage","url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/11\/lpk1a.jpg","contentUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/11\/lpk1a.jpg","width":222,"height":189},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/immune-cell-policing-offers-insights-cancer-autoimmune-disease\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"Immune cell policing offers insights into cancer, autoimmune disease"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","description":"The Power of Science","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"zh-CN"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"zh-CN","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"gallery":false,"paper_url":"http:\/\/www.pnas.org\/content\/114\/47\/12542","journal_title":"Proceedings of the National Academy of Sciences","paper_author_list":"Nanhai He, Weiwei Fan, Brian Henriquez, Ruth T. Yu, Annette R. Atkins, Christopher Liddle, Ye Zheng, Michael Downes, and Ronald M. Evans","paper_title":"Metabolic control of regulatory T cell (Treg) survival and function by Lkb1","subhead":"","home_photo":"","listing_photo":"","legacy_boilerplate":[],"hide_boilerplate":[],"disable_date":false,"listing_excerpt":"","descriptive_blurb":"","has_journal_cover":false,"doi":"","og_image_override":false},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/15316","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":15,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/15316\/revisions"}],"predecessor-version":[{"id":16593,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/15316\/revisions\/16593"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/media\/15377"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/media?parent=15316"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/faculty?post=15316"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disease-research?post=15316"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}