{"id":45213,"date":"2025-10-11T00:48:39","date_gmt":"2025-10-10T22:48:39","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/10\/11\/p38-signaling-enhances-short-lived-effector-cell-differentiation-and-weakens-central-memory-cd8-t-cell-formation\/"},"modified":"2025-10-11T00:48:39","modified_gmt":"2025-10-10T22:48:39","slug":"p38-signaling-enhances-short-lived-effector-cell-differentiation-and-weakens-central-memory-cd8-t-cell-formation","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/10\/11\/p38-signaling-enhances-short-lived-effector-cell-differentiation-and-weakens-central-memory-cd8-t-cell-formation\/","title":{"rendered":"p38 signaling enhances short-lived effector cell differentiation and weakens central memory CD8+ T-cell formation"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Oct 10:vkaf214. doi: 10.1093\/jimmun\/vkaf214. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Memory CD8+ T cells are essential for long-term protective immunity. Here, we show that activation of p38 MAPK during the primary response of CD8+ T cells orchestrates a delicate balance between the formation of short-lived effector cells and memory precursor effector cells. p38\u03b1fl\/flp38\u03b2fl\/flGzmBcre\/- mice, in which p38\u03b1 and p38\u03b2 were efficiently deleted in CD8+ T cells and also in early stages of T-cell development, were used in studying the role of the p38 pathway in T cells. The deletion of p38\u03b1 and p38\u03b2 (simplified as p38\u03b1\/\u03b2) has very minor effects on thymic and peripheral T-cell development. In contrast, p38\u03b1\/\u03b2-deficient CD8+ T cells were skewed toward a central memory phenotype and mounted stronger recall responses upon secondary challenge. Transcriptomic analyses of antigen-specific CD8+ T cells revealed that p38\u03b1\/\u03b2 deficiency is associated with reduced effector gene expression and enhanced memory-associated programs. Furthermore, in vitro differentiated p38\u03b1\/\u03b2-deficient CD8+ T cells showed superior persistence and functional responses after adoptive transfer. These results establish a role for p38 in controlling effector CD8+ T-cell differentiation and memory formation, and reinforce the therapeutic potential of targeting this pathway, aligning with recent studies demonstrating the beneficial effects of p38 inhibitors in adoptive cell therapy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41071826\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20251010184839&amp;v=2.18.0.post9+e462414\">41071826<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf214\">10.1093\/jimmun\/vkaf214<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Oct 10:vkaf214. doi: 10.1093\/jimmun\/vkaf214. Online ahead of print. ABSTRACT Memory CD8+ T cells are essential for long-term protective immunity. Here, we show that activation of p38 MAPK during the primary response of CD8+ T cells orchestrates a delicate balance between the formation of short-lived effector cells and memory precursor effector cells. p38\u03b1fl\/flp38\u03b2fl\/flGzmBcre\/- &#8230; <a title=\"p38 signaling enhances short-lived effector cell differentiation and weakens central memory CD8+ T-cell formation\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/10\/11\/p38-signaling-enhances-short-lived-effector-cell-differentiation-and-weakens-central-memory-cd8-t-cell-formation\/\" aria-label=\"Read more about p38 signaling enhances short-lived effector cell differentiation and weakens central memory CD8+ T-cell formation\">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-45213","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\/45213","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=45213"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/45213\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=45213"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=45213"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=45213"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}