{"id":71350,"date":"2026-07-23T12:30:33","date_gmt":"2026-07-23T10:30:33","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/07\/23\/gammaherpesvirus-infection-impairs-lung-fibrosis-resolution-through-pd-l1-fibroblasts-and-pd-1-cd8-t-cell-interaction-laura-kempen\/"},"modified":"2026-07-23T12:30:33","modified_gmt":"2026-07-23T10:30:33","slug":"gammaherpesvirus-infection-impairs-lung-fibrosis-resolution-through-pd-l1-fibroblasts-and-pd-1-cd8-t-cell-interaction-laura-kempen","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/07\/23\/gammaherpesvirus-infection-impairs-lung-fibrosis-resolution-through-pd-l1-fibroblasts-and-pd-1-cd8-t-cell-interaction-laura-kempen\/","title":{"rendered":"Gammaherpesvirus infection impairs lung fibrosis resolution through PD-L1+ fibroblasts and PD-1+ CD8+ T cell interaction. Laura Kempen"},"content":{"rendered":"<div>\n<p><b>Mucosal Immunol<\/b>. 2026 Jul 22:100388. doi: 10.1016\/j.mucimm.2026.100388. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Pulmonary fibrosis is a complex disease with poorly understood, multifactorial triggers. Gammaherpesviruses (\u03b3HVs), including Epstein-Barr virus in humans and Murid herpesvirus 4 (MuHV-4) in mice, have been linked to pulmonary fibrosis exacerbation, although the underlying mechanisms remain unclear. This study explores how \u03b3HV infection modulates bleomycin (bleo)-induced lung fibrosis in mice, using flow cytometry and multiplex spectral immunofluorescence (MSI) to analyze cell dynamics, localization, and intercellular crosstalk. Despite the substantial contribution of monocytes (MOs) to the alveolar macrophage (AM) pool following MuHV-4 infection, these cells do not exhibit overt profibrotic properties upon bleo treatment. In contrast, MuHV-4 infection led to the accumulation of activated, IFN\u03b3-producing memory CD8<sup>+<\/sup> T cells in the lungs of bleo-treated mice, with MSI revealing their enrichment and colocalization with fibroblasts. Notably, fibroblasts showed increased IFN\u03b3-induced PD-L1 expression, while T cells upregulated PD-1, co-localizing in fibrosis-rich regions. In vivo neutralization of the PD-L1\/PD-1 axis after bleo treatment significantly improved the resolution of fibrosis in MuHV-4-infected mice, highlighting the key pathogenic role of this interaction in sequelae persistence. Compared to fibroblasts cocultured with T cells from na\u00efve mice, those cocultured with MuHV-4-induced T cells exhibited significantly increased collagen expression, while this effect was abrogated by PD-1 blockade. Similar results were observed in cocultures of human fibroblasts and CD8<sup>+<\/sup> T cells isolated from EBV-infected patients, underscoring the translational potential of these findings. Collectively, our findings identify interactions between PD-1<sup>+<\/sup> CD8<sup>+<\/sup> T cells and PD-L1<sup>+<\/sup> fibroblasts as central drivers of persistent lung fibrosis associated with \u03b3HV infection.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42486432\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20260723063033&amp;v=2.20.0\">42486432<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2026.100388\">10.1016\/j.mucimm.2026.100388<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2026 Jul 22:100388. doi: 10.1016\/j.mucimm.2026.100388. Online ahead of print. ABSTRACT Pulmonary fibrosis is a complex disease with poorly understood, multifactorial triggers. Gammaherpesviruses (\u03b3HVs), including Epstein-Barr virus in humans and Murid herpesvirus 4 (MuHV-4) in mice, have been linked to pulmonary fibrosis exacerbation, although the underlying mechanisms remain unclear. This study explores how \u03b3HV &#8230; <a title=\"Gammaherpesvirus infection impairs lung fibrosis resolution through PD-L1+ fibroblasts and PD-1+ CD8+ T cell interaction. Laura Kempen\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/07\/23\/gammaherpesvirus-infection-impairs-lung-fibrosis-resolution-through-pd-l1-fibroblasts-and-pd-1-cd8-t-cell-interaction-laura-kempen\/\" aria-label=\"Read more about Gammaherpesvirus infection impairs lung fibrosis resolution through PD-L1+ fibroblasts and PD-1+ CD8+ T cell interaction. Laura Kempen\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[57,42],"tags":[],"class_list":["post-71350","post","type-post","status-publish","format-standard","hentry","category-mucosal-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/71350","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=71350"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/71350\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=71350"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=71350"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=71350"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}