{"id":57822,"date":"2026-03-08T00:52:08","date_gmt":"2026-03-07T23:52:08","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/08\/pd-l1-cell-intrinsic-signals-limit-immune-activation-during-cutaneous-vaccinia-virus-infection\/"},"modified":"2026-03-08T00:52:08","modified_gmt":"2026-03-07T23:52:08","slug":"pd-l1-cell-intrinsic-signals-limit-immune-activation-during-cutaneous-vaccinia-virus-infection","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/08\/pd-l1-cell-intrinsic-signals-limit-immune-activation-during-cutaneous-vaccinia-virus-infection\/","title":{"rendered":"PD-L1 cell-intrinsic signals limit immune activation during cutaneous vaccinia virus infection"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Feb 9;215(2):vkaf368. doi: 10.1093\/jimmun\/vkaf368.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Negative T-cell regulation through programmed cell death 1 (PD-1)-programmed death ligand 1 (PD-L1) ligation is well described during viral infection; however, our understanding of the contribution of PD-L1-intrinsic signaling to antiviral immunity is limited. Herein, we show that mutation of the PD-L1 intracellular domain results in a dysregulated type 1 interferon (IFN) response in dendritic cells (DCs), sustained DC activation, and higher skin DC retention during vaccinia virus (VV) scarification of the ear. Consequently, in mice with a mutation in the cytoplasmic domain of PD-L1, we observed decreased CD8+ T-cell responses in the lymph node with enhanced CD8+ T-cell proliferation and cytokine production in the tissue. Eliminating the effect of decreased DC migration to the draining lymph node with systemic VV inoculation resulted in increased CD8+ T-cell responses after a subsequent local infection of the ear tissue. Responding CD8+ T cells in the ear displayed an increased ability to produce IFN-\u03b3 that was dependent on cDC1s. During VV rechallenge in the mice with a mutation in the cytoplasmic domain of PD-L1, the local memory CD8+ T cells showed increased cytokine production, concurrent with increased tissue swelling. Taken together, these findings establish PD-L1-intrinsic signaling as an important regulator of DC activation and migration and defines the consequences for increased T-cell residency and activity in the tissue in the absence of PD-L1-intrinsic signals.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41793774\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260307185157&amp;v=2.19.0.post6+133c1fe\">41793774<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf368\">10.1093\/jimmun\/vkaf368<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Feb 9;215(2):vkaf368. doi: 10.1093\/jimmun\/vkaf368. ABSTRACT Negative T-cell regulation through programmed cell death 1 (PD-1)-programmed death ligand 1 (PD-L1) ligation is well described during viral infection; however, our understanding of the contribution of PD-L1-intrinsic signaling to antiviral immunity is limited. Herein, we show that mutation of the PD-L1 intracellular domain results in a &#8230; <a title=\"PD-L1 cell-intrinsic signals limit immune activation during cutaneous vaccinia virus infection\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/03\/08\/pd-l1-cell-intrinsic-signals-limit-immune-activation-during-cutaneous-vaccinia-virus-infection\/\" aria-label=\"Read more about PD-L1 cell-intrinsic signals limit immune activation during cutaneous vaccinia virus infection\">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-57822","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\/57822","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=57822"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/57822\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=57822"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=57822"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=57822"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}