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Recent studies have shown that pharmacotherapy for GVHD should target both the innate and adaptive inflammatory immune responses. Juglone, a redox\u2010active phytochemical found in walnuts, has shown potent anti\u2010inflammatory effects in models of colitis and inflammatory bowel disease. However, its effects on T\u2010cell\u2010mediated immune responses remain largely unknown. Considering the overlapping mediators of inflammation in GVHD and the aforementioned conditions, we investigated the use of juglone as a prophylactic agent for GVHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Immunomodulatory activity and mechanism of action of juglone were studied using murine splenic leukocytes in vitro. The GVHD prophylactic efficacy of orally administered juglone was evaluated using a murine model of allogeneic haematopoietic stem cell transplantation based on an MHC mismatch.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Juglone exhibited immunomodulatory activity by (i) inhibiting the activation of dendritic cells and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells, (ii) inhibiting cytokine secretion and lymphocyte proliferation, and (iii) inducing exhaustion of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cells, as shown by increased expression of CTLA\u20104 (CD152) and Fas (CD95). Oral administration of juglone significantly reduced mortality and morbidity associated with GVHD while maintaining graft\u2010versus\u2010leukaemia activity. This was accompanied by a decrease in the number of na\u00efve CD4\n                      <jats:sup>+<\/jats:sup>\n                      cells, and an increase in the number of CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      central memory T\u2010cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Juglone is a potent immunomodulator for GVHD prophylaxis. Our study is the first to provide a dosage framework for the oral administration of juglone that can be used for clinical development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LINKED ARTICLES<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed issue Recent Innovations in Targeting Redox Biology for Therapeutics. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v183.1\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v183.1\/issuetoc<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16350","type":"journal-article","created":{"date-parts":[[2024,4,7]],"date-time":"2024-04-07T21:25:05Z","timestamp":1712525105000},"page":"131-152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunomodulation by juglone alleviates acute graft\u2010versus\u2010host disease without compromising the graft\u2010versus\u2010leukaemia activity in mice"],"prefix":"10.1111","volume":"183","author":[{"given":"Dievya","family":"Gohil","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre  Navi Mumbai India"},{"name":"Training School Complex Homi Bhabha National Institute  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khushboo A.","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre  Navi Mumbai India"},{"name":"Training School Complex Homi Bhabha National Institute  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saurabh Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre  Navi Mumbai India"},{"name":"Training School Complex Homi Bhabha National Institute  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poonam","family":"Gera","sequence":"additional","affiliation":[{"name":"ICGC Lab, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre  Navi Mumbai India"},{"name":"Biorepository, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre  Navi Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subhash","family":"Yadav","sequence":"additional","affiliation":[{"name":"Training School Complex Homi Bhabha National Institute  Mumbai India"},{"name":"Department of Pathology, Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre  Navi Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raghavendra","family":"Patwardhan","sequence":"additional","affiliation":[{"name":"Training School Complex Homi Bhabha National Institute  Mumbai India"},{"name":"Radiation Biology &amp; 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