{"id":64700,"date":"2026-05-15T12:37:53","date_gmt":"2026-05-15T10:37:53","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/05\/15\/ndrg3-is-essential-for-sustaining-antigen-driven-t-cell-responses-by-protecting-against-restimulation-induced-cell-death\/"},"modified":"2026-05-15T12:37:53","modified_gmt":"2026-05-15T10:37:53","slug":"ndrg3-is-essential-for-sustaining-antigen-driven-t-cell-responses-by-protecting-against-restimulation-induced-cell-death","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/05\/15\/ndrg3-is-essential-for-sustaining-antigen-driven-t-cell-responses-by-protecting-against-restimulation-induced-cell-death\/","title":{"rendered":"NDRG3 is essential for sustaining antigen-driven T cell responses by protecting against restimulation-induced cell death"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 May 14;215(5):vkag070. doi: 10.1093\/jimmun\/vkag070.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>During the response to infections and pathogenic challenges, T cells must expand profoundly and be resilient to repetitive restimulation to clear the ongoing assault and protect the host. This process of prolific expansion is tightly regulated to quickly provide a robust pool of pathogen-fighting T cells, yet also limit excessive expansion to prevent inadvertent damage to host tissues. Restimulation-dependent pro-growth and pro-death signals help regulate this delicate balance of T cell expansion to maintain both host and T cell homeostasis. We have discovered that NDRG3 is a critical determinant of whether T cells proliferate or undergo apoptosis during repetitive restimulation under antigen-driven T cell expansion. CD8+ T cells lacking NDRG3 exhibit severely impaired expansion in vivo in response to both viral infections and tumor challenges. We show that NDRG3 is essential for T cell survival during antigen restimulation by protecting T cells from restimulation-induced cell death (RICD), while it has only a marginal impact on T cell survival in contexts with limited antigen restimulation. Mechanistically, NDRG3 safeguards repetitively stimulated T cells from RICD by constraining FAS-mediated pro-death signaling through caspase-8. Furthermore, NDRG3 overexpression enhanced T cell infiltration into tumors, improving their tumor-controlling capacity. Collectively, these findings establish NDRG3 as a novel, indispensable regulator of T cell responses to foreign challenges. Additionally, this work identifies NDRG3 as a previously undescribed regulator of RICD in T cells and reveals NDRG3 as a potential target for autoimmune disorders and chimeric antigen receptor T cell treatment for cancer.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42136568\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260515063752&amp;v=2.20.0\">42136568<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag070\">10.1093\/jimmun\/vkag070<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 May 14;215(5):vkag070. doi: 10.1093\/jimmun\/vkag070. ABSTRACT During the response to infections and pathogenic challenges, T cells must expand profoundly and be resilient to repetitive restimulation to clear the ongoing assault and protect the host. This process of prolific expansion is tightly regulated to quickly provide a robust pool of pathogen-fighting T cells, yet &#8230; <a title=\"NDRG3 is essential for sustaining antigen-driven T cell responses by protecting against restimulation-induced cell death\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/05\/15\/ndrg3-is-essential-for-sustaining-antigen-driven-t-cell-responses-by-protecting-against-restimulation-induced-cell-death\/\" aria-label=\"Read more about NDRG3 is essential for sustaining antigen-driven T cell responses by protecting against restimulation-induced cell death\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-64700","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/64700","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=64700"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/64700\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=64700"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=64700"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=64700"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}