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Myeloid cells phagocytose these CNPs, undergo apoptosis, and release oxidized DNA, including 8-hydroxy-2′-deoxyguanosine. Antigen-specific CNP treatment increases PD-L1+ dendritic cells and FoxP3+, CTLA-4+, PD-1+, and IL-10+ regulatory CD4+ T cells through an STING/IFNAR-dependent mechanism, extending to tolerance induced by both apoptotic leukocytes and red blood cell therapies.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/stingtype-i-interferon-pathway-is-required-for-antigen-containing-plga-nanoparticle-and-apoptotic-cellinduced-cd4-t-cell-tolerance/419246/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/stingtype-i-interferon-pathway-is-required-for-antigen-containing-plga-nanoparticle-and-apoptotic-cellinduced-cd4-t-cell-tolerance/419246.png","ImageObject",300,407,{"name":92,"@type":93},"Đào","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What question does the study address about CNP-induced tolerance?","Question",{"text":113,"@type":114},"It identifies the cellular and molecular pathways responsible for antigen-specific tolerogenic immune-modifying particle responses that were previously observed but not mechanistically understood.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do myeloid cells interact with antigen-containing CNPs in the proposed mechanism?",{"text":118,"@type":114},"Myeloid cells phagocytose the CNPs, undergo apoptosis, and release oxidized DNA, including 8-hydroxy-2′-deoxyguanosine.",{"name":120,"@type":111,"acceptedAnswer":121},"Which signaling pathway is required for antigen-specific CD4+ T cell tolerance?",{"text":122,"@type":114},"The study shows the STING/type I interferon axis, specifically a STING/IFNAR-dependent pathway, is required for tolerance induced by apoptotic cells and CNP-induced apoptosis.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},419246,1790736234,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1374402968488,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","IMMUNOLOGY  \nSTING/type I interferon pathway is required for antigen-containing PLGA nanoparticle-andapoptotic cell–induced CD4+T cell tolerance  \nJoseph R. Podojil1,2,3†, Andrew C. Cogswell1,2†, Tobias Neef1, Ming-Yi Chiang1, Sara A. Beddow1, Gabriel Arellano1, Sandeep Kakade3, Derrick P. McCarthy1,3, Adam Elhofy3, ChrisT. Harp1, Mairah Khan4, Joshua J. Meeks4, Dan Xu1, Lonnie D. Shea5, Stephen D. Miller1,2*  \nAutoreactive CD4+ T cell infiltration, tissue destruction, and spread epitope–specific CD4+ T cell activation underly CD4+ T cell–mediated autoimmune disease pathogenesis. Here, we identify previously unknown pathways required for antigen (Ag)–specific tolerogenic immune-modifying particle/Cour nanoparticle (TIMP/CNP)–induced tolerance. The data show that myeloid cells phagocytose CNPs, undergo apoptosis, and release oxidized DNA [8-hydroxy-2′-deoxyguanosine (8-OHG)]. Subsequently, Ag-specific CNP treatment increases the number of PD-L1+ cDC2 dendritic cells and the number of FoxP3+, CTLA-4+, PD-1+, and IL-10+ regulatory CD4+ T cells via a stimulatorof interferon genes (STING)/interferon-α/β receptor (IFNAR)–dependent pathway. In addition, these same pathways were found to be required for both Ag-coupled apoptotic leukocyte–induced and Ag-coupled red blood cell treatment–induced CD4+ T cell tolerance. Together, these results show that Ag-specific tolerance induced by the presence of apoptotic cells, and by CNP-induced apoptosis, requires the STING/IFNAR pathway, thereby illustrating a previously unknown function of this pathway.  \ncopyright © 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S.  \nGovernment Works. distributed under a creative commons Attribution license 4.0 (cc BY) .  \nINTRODUCTION  \nAutoimmune diseases are characterized by a failure of immune regulation, resulting in the destruction of self-tissue by autoreactive T cells. Thus, numerous immunosuppressive therapies targeting T cell activation, migration, and function are standard practice for treating autoimmune diseases (1). We previously reported that tolerance induced by intravenous administration of proteins/peptides cross-linked, using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), to syngeneicapoptotic splenic leukocytes or red blood cells (RBCs) safely and efficiently induced antigen (Ag)–specific immune tolerance. Treatment has been shown tobe functional for both the prevention and therapeutic treatment ofT helper type 1 cell (TH 1 cell)– and TH 17 cell–mediated autoimmune diseases (2–4). This strategy proved to be both safe and able to decrease Ag-specific CD4+ T cell responses to myelin peptidesex vivo in a phase 1 clinical trial in patients with multiple sclerosis (MS)  \n(5). However, the manufacturing process for this tolerance inducing approach is complex and expensive because autologous leukocytes must be isolated and peptide coupled under good manufacturing practice conditions before reinfusion. To overcome the cost and complexity of this cell-based approach, we established a tolerance methodology using intravenous delivery of proteins/peptides associated with 500-nm carboxylated “biodegradable” poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles, i.e., tolerogenic immune-modifying particles (TIMPs), also referred to as Cour nanoparticles (CNPs) . CNPs serve as an effective method for inducing robust Ag-specific tolerance for the prevention and treatment of the experimental autoimmune encephalomyelitis (EAE) model ofMS and the nonobese diabetic (NOD) model  \n1department of Microbiology-immunology, northwestern University, chicago, il, USA. 2center for human immunobiology, northwestern University, chicago, il, USA. 3cour Pharmaceutical development company, Skokie, il, USA. 4Urology Feinberg School of Medicine, northwestern University, chicago, il, USA. 5department of Biomedical engineering, University of Michigan, Ann Arbor, Mi, USA.  \n*[correspon","cbCaieqn9Hk7Sc3X","https://ap.wps.com/l/cbCaieqn9Hk7Sc3X","pdf",6635842,"English","# Introduction\n## Autoimmune disease and immune regulation failure\n## Prior tolerance approaches using cross-linked proteins/peptides\n## Development of tolerogenic immune-modifying particles (TIMPs/CNPs)\n## Clinical translation and early trial outcomes\n## Knowledge gap in mechanisms of CNP- and leukocyte-induced tolerance\n## cGAS/STING as an innate DNA-sensing pathway","[{\"question\":\"What question does the study address about CNP-induced tolerance?\",\"answer\":\"It identifies the cellular and molecular pathways responsible for antigen-specific tolerogenic immune-modifying particle responses that were previously observed but not mechanistically understood.\"},{\"question\":\"How do myeloid cells interact with antigen-containing CNPs in the proposed mechanism?\",\"answer\":\"Myeloid cells phagocytose the CNPs, undergo apoptosis, and release oxidized DNA, including 8-hydroxy-2′-deoxyguanosine.\"},{\"question\":\"Which signaling pathway is required for antigen-specific CD4+ T cell tolerance?\",\"answer\":\"The study shows the STING/type I interferon axis, specifically a STING/IFNAR-dependent pathway, is required for tolerance induced by apoptotic cells and CNP-induced apoptosis.\"}]","STING/type I interferon pathway is required for antigen-containing PLGA nanoparticle-and apoptotic cell–induced CD4+ T cell tolerance | PDF",1790616298,48]