{"id":4866,"date":"2025-06-19T17:24:00","date_gmt":"2025-06-19T15:24:00","guid":{"rendered":"https:\/\/www.sfb274.de\/?p=4866"},"modified":"2025-11-07T12:28:11","modified_gmt":"2025-11-07T11:28:11","slug":"tgf%ce%b1-controls-checkpoints-in-cns-resident-and-infiltrating-immune-cells","status":"publish","type":"post","link":"https:\/\/www.sfb274.de\/en\/tgf%ce%b1-controls-checkpoints-in-cns-resident-and-infiltrating-immune-cells\/","title":{"rendered":"TGF\u03b1 controls checkpoints in CNS resident and infiltrating immune cells to promote resolution of inflammation"},"content":{"rendered":"\n<p><strong>Background<\/strong><\/p>\n\n\n\n<p>Autoimmune inflammation in the central nervous system (CNS), such as in multiple sclerosis (MS), causes varying outcomes largely influenced by complex interactions among resident glial cells (microglia, astrocytes), infiltrating immune cells, and the blood\u2013brain barrier. Understanding the endogenous mechanisms that drive inflammation resolution and tissue repair is essential, but these CNS-intrinsic pathways remain poorly defined.<\/p>\n\n\n\n<div class=\"wp-block-group has-theme-palette-8-background-color has-background\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<p><strong>Key Findings<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Microglia-Derived TGF\u03b1 as a Central Regulator<\/strong>: Microglia in both human MS cerebrospinal fluid (CSF) and a mouse model of MS (EAE) were shown to secrete TGF\u03b1 with tightly controlled timing and localization, especially during recovery phases.<\/li>\n\n\n\n<li><strong>Multi-Cellular Protective Effects<\/strong>: Genetic removal of TGF\u03b1 in microglia aggravated EAE severity, increased CNS infiltration by T cells and myeloid cells, and led to greater neuron and oligodendrocyte loss, demyelination, and axonal injury. <br>In vitro, TGF\u03b1 reduced inflammatory gene expression in microglia, astrocytes, macrophages, dendritic cells, oligodendrocyte precursors, and neurons, highlighting its broad anti-inflammatory and neuroprotective properties.<\/li>\n\n\n\n<li><strong>Intranasal TGF\u03b1 as a Therapeutic Strategy<\/strong>: Delivering TGF\u03b1 intranasally in EAE mice improved clinical outcomes, decreased lesion volumes (confirmed by MRI), balanced immune signaling in astrocytes and T cells, reduced glial reactivity, and preserved neurons and myelin integrity.<br>Reduced CSF TGF\u03b1 levels were observed in relapsing-remitting MS patients, inversely correlated with clinical severity, suggesting that boosting TGF\u03b1 may help restore protective immune networks .<\/li>\n<\/ul>\n<\/div><\/div>\n\n\n\n<p><strong>Implications<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>TGF\u03b1 emerges as a key mediator of glial\u2013immune crosstalk<\/strong>, regulating infiltrating immune cells and supporting CNS-resident cells during recovery.<\/li>\n\n\n\n<li><strong>Targeting TGF\u03b1 may represent a novel therapeutic Avenue<\/strong>: Intranasal delivery that bypasses the blood\u2013brain barrier could leverage endogenous tissue repair mechanisms, offering a new direction for treating acute and progressive neuroinflammatory disorders like MS.<\/li>\n<\/ul>\n\n\n\n<p><strong>Conclusion<\/strong><\/p>\n\n\n\n<p>This study uncovers microglia-derived TGF\u03b1 as a powerful, multi-targeted agent that orchestrates CNS recovery after autoimmune inflammation. By dampening inflammation and promoting survival of neurons and oligodendrocytes, TGF\u03b1 holds significant therapeutic promise, especially when delivered intranasally to enhance lesion resolution and protect neural tissue.<\/p>\n\n\n\n<p><strong>\ud83d\udcd6 Full text for further details:<\/strong> <a href=\"https:\/\/www.nature.com\/articles\/s41467-025-60363-7\" target=\"_blank\" rel=\"noreferrer noopener\">Nature Communications<\/a><\/p>\n\n\n\n<p>TRR 274 Project leaders contributing to this project:&nbsp;<strong>Veit Rothammer<\/strong> (1st Funding Period &#8211; B04: Interaction of glial and CNS infiltrating immune cells in the recovery from acute inflammatory and hypoxic tissue damage in the CNS).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Background Autoimmune inflammation in the central nervous system (CNS), such as in multiple sclerosis (MS), causes varying outcomes largely influenced by complex interactions among resident glial cells (microglia, astrocytes), infiltrating immune cells, and the blood\u2013brain barrier. Understanding the endogenous mechanisms that drive inflammation resolution and tissue repair is essential, but these CNS-intrinsic pathways remain poorly&#8230;<\/p>\n","protected":false},"author":4,"featured_media":4868,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_kad_blocks_custom_css":"","_kad_blocks_head_custom_js":"","_kad_blocks_body_custom_js":"","_kad_blocks_footer_custom_js":"","_kad_post_transparent":"","_kad_post_title":"","_kad_post_layout":"","_kad_post_sidebar_id":"","_kad_post_content_style":"","_kad_post_vertical_padding":"","_kad_post_feature":"","_kad_post_feature_position":"","_kad_post_header":false,"_kad_post_footer":false,"footnotes":""},"categories":[33],"class_list":["post-4866","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-other"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.7 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>TGF\u03b1 controls checkpoints in CNS resident and infiltrating immune cells to promote resolution of inflammation - 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