{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:26:24Z","timestamp":1787772384890,"version":"build-2784847793"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVES:<\/jats:title>\n                    <jats:p>\n                      Psoriasis is a chronic infectious skin disease triggered by an autoimmune process involving T-cell-mediated hyper-proliferation of keratinocytes. The objective of this study is to assess the modulation of programmed death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) through JAK\/STAT pathway during the development of a psoriasis-like disease by both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      model. Baricitinib, a known inhibitor of JAK1 and JAK2, was used to study the impact on PD-1 and PD-L1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS:<\/jats:title>\n                    <jats:p>Human peripheral blood mononuclear cells (PBMC) were stimulated with either anti-CD3\/CD28 or PMA\/Ionomycin, to modulate level of PD-1 and PD-L1 under psoriasis-like condition. Interferon-gamma (IFN\u03b3) was used to treat HaCaT cells to mimic the diseased keratinocytes found in Psoriatic patients. Psoriasis was induced with Imiquimod (IMQ) in animal model to study the cross-talk between different cell types and pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Expression levels of PD-1 and PD-L1 in PBMC, and secretion of cytokines, namely tumor necrosis factor-\u03b1 (TNF\u03b1), IFN\u03b3, interleukin (IL)-6, and IL-1 \u03b2, were down-regulated on treatment with baricitinib. Further, in IFN\u03b3-treated HaCaT cells (keratinocytes) mRNA levels of KRT-17 and PD-L1 were up-regulated.). Interestingly, in IFN\u03b3-treated HaCat cells baricitinib decreased the levels of inflammatory cytokines such as IL-1 \u03b2, IL-6, and TNF\u03b1 along with KRT-17 and PD-L1. On IFN\u03b3-treatment. Data from both PBMC and HaCaT suggest an anti-inflammatory role for this compound. Accordingly, baricitinib was able to alleviate disease symptom in IMQ induce mice model of psoriasis. As a consequence of baricitinib treatment down-regulation of p-STAT3, PD- and PD-L1 expression levels were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION:<\/jats:title>\n                    <jats:p>This study demonstrates a crosstalk between JAK\/STAT and PD-1\/PD-L1 pathways. It also demonstrates that cytokines such as IFN\u03b3 and IL-17 are down-regulated by baricitinib. We believe decreased expressions of PD-1 and PD-L1 may be a consequence of baricitinib-induced down-regulation of IFN\u03b3 and IL-17. More importantly, our data from the acute model of psoriasis indicates that PD-L1 behaves as a T-cell-associated T-cell-associated surrogate activation marker rather than immunosuppressive marker in early phase of psoriasis. Therefore it does not exhibit a causal relationship to disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijp.ijp_1089_20","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T15:51:03Z","timestamp":1716479463000},"page":"183-193","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Effect of baricitinib in regulating programmed death 1 and ligand programmed cell death ligand 1 through JAK\/STAT pathway in psoriasis"],"prefix":"10.4103","volume":"54","author":[{"given":"H. 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