{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:48:14Z","timestamp":1782744494303,"version":"3.54.5"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Beh\u00e7et\u2019s disease (BD) is a systemic vasculitis with inflammatory lesions mediated by cytotoxic T cells and neutrophils. Here, we explore the critical involvement of NF-\u03baB signaling pathway in proinflammatory CD8+ T cells differentiation and disease progress of BD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed microarray gene expression analyses, flow cytometry, immunophenotyping, immunohistochemistry and functional assessments of CD8+ T cells from BD patients and HD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptionally, among the 6,595 up-regulated genes in CD8+ T cells of BD vs HD, we highlighted a great enrichment for pathways linked to NF-\u03baB and TLR signaling (i.e.\n                      <jats:italic>NFKB1<\/jats:italic>\n                      ,\n                      <jats:italic>RELB<\/jats:italic>\n                      ,\n                      <jats:italic>REL<\/jats:italic>\n                      ,\n                      <jats:italic>TLR1<\/jats:italic>\n                      ,\n                      <jats:italic>IRF4)<\/jats:italic>\n                      . Phenotypically, CD8+ T cells from BD had a higher expression of phosphorylated NF-\u03baB (pNF-\u03baB, 4.4 \u00b1 0.9\n                      <jats:italic>vs.<\/jats:italic>\n                      1.8 \u00b1 0.2 in MFI, p = 0.001), were more activated (higher CD11c, CD11b, CD25 and TNF-\u03b1, IFN-\u03b3 expression) and exhibited more expression of Perforin and Granzyme B (33% \u00b1 9\n                      <jats:italic>vs<\/jats:italic>\n                      . 9 \u00b1 5, p = 0.009, 47% \u00b1 8\n                      <jats:italic>vs.<\/jats:italic>\n                      21% \u00b1 6, p = 0.02, respectively) as compared to HD. Phosphodiesterase-4 (PDE4), an immune cell enzyme that activate the NF-\u03baB pathway was up-regulated in blood and skin lesions of BD.\n                      <jats:italic>In vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      inhibition of PDE4 strongly inhibited CD8+ T cell activation, cytokine secretion, cytotoxicity and proliferation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We highlighted that activated CD8+ T cells through NF-\u03baB signaling pathway are instrumental in BD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1834685","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:34:17Z","timestamp":1782743657000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PDE4 inhibitor mitigates activated CD8+ T cells through NF-\u03baB signaling in Beh\u00e7et\u2019s syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Alexandre","family":"Le Joncour","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMR S 959, Immunology-Immunopathology- Immunotherapy (I3); Laboratoire d\u2019excellence TRANSIMMUNOM, RHU iMAP","place":["Paris, France"]},{"name":"Biotherapy (CIC-BTi), H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, AP-HP","place":["Paris, France"]},{"name":"Department of Internal Medicine and Clinical immunology, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, AP-HP","place":["Paris, 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