{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:20:35Z","timestamp":1780503635651,"version":"3.54.1"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medicine Healthy Longevity Translational Research Program","award":["R-183-000-434-133"],"award-info":[{"award-number":["R-183-000-434-133"]}]},{"name":"USPC-SPO-NUS project","award":["R-183-000-434-133"],"award-info":[{"award-number":["R-183-000-434-133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Graft-versus-host disease (GVHD) is a life-threatening systemic complication of allogeneic hematopoietic stem cell transplantation (HSCT) characterized by dysregulation of T and B cell activation and function, scleroderma-like features, and multi-organ pathology. The treatment of cGVHD is limited to the management of symptoms and long-term use of immunosuppressive therapy, which underscores the need for developing novel treatment approaches. Notably, there is a striking similarity between cytokines\/chemokines responsible for multi-organ damage in cGVHD and pro-inflammatory factors, immune modulators, and growth factors secreted by senescent cells upon the acquisition of senescence-associated secretory phenotype (SASP). In this pilot study, we questioned the involvement of senescent cell-derived factors in the pathogenesis of cGVHD triggered upon allogeneic transplantation in an irradiated host. Using a murine model that recapitulates sclerodermatous cGVHD, we investigated the therapeutic efficacy of a senolytic combination of dasatinib and quercetin (DQ) administered after 10 days of allogeneic transplantation and given every 7 days for 35 days. Treatment with DQ resulted in a significant improvement in several physical and tissue-specific features, such as alopecia and earlobe thickness, associated with cGVHD pathogenesis in allograft recipients. DQ also mitigated cGVHD-associated changes in the peripheral T cell pool and serum levels of SASP-like cytokines, such as IL-4, IL-6 and IL-8R\u03b1. Our results support the involvement of senescent cells in the pathogenesis of cGVHD and provide a rationale for the use of DQ, a clinically approved senolytic approach, as a potential therapeutic strategy.<\/jats:p>","DOI":"10.3390\/biology12050647","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T02:06:35Z","timestamp":1682388395000},"page":"647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic Potential of a Senolytic Approach in a Murine Model of Chronic GVHD"],"prefix":"10.3390","volume":"12","author":[{"given":"Deepika","family":"Raman","sequence":"first","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Ch\u00eane","sequence":"additional","affiliation":[{"name":"D\u00e9partement 3I, Infection, Immunit\u00e9 et Inflammation, Institut Cochin, INSERM U1016, Universit\u00e9 de Paris, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8211-2556","authenticated-orcid":false,"given":"Carole","family":"Nicco","sequence":"additional","affiliation":[{"name":"D\u00e9partement 3I, Infection, Immunit\u00e9 et Inflammation, Institut Cochin, INSERM U1016, Universit\u00e9 de Paris, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Jeljeli","sequence":"additional","affiliation":[{"name":"D\u00e9partement 3I, Infection, Immunit\u00e9 et Inflammation, Institut Cochin, INSERM U1016, Universit\u00e9 de Paris, 75014 Paris, France"},{"name":"Universit\u00e9 de Paris, Facult\u00e9 de M\u00e9decine, AP-HP-Centre Universit\u00e9 de Paris, H\u00f4pital Cochin, Service d\u2019Immunologie Biologique, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie Qing","family":"Eu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"},{"name":"Cancer Science Institute, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9442-9382","authenticated-orcid":false,"given":"Marie-V\u00e9ronique","family":"Cl\u00e9ment","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"},{"name":"NUS Medicine Healthy Longevity Program, National University of Singapore, Singapore 117597, Singapore"},{"name":"Integrated Science and Engineering Program, NUS Graduate School, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Batteux","sequence":"additional","affiliation":[{"name":"D\u00e9partement 3I, Infection, Immunit\u00e9 et Inflammation, Institut Cochin, INSERM U1016, Universit\u00e9 de Paris, 75014 Paris, France"},{"name":"Universit\u00e9 de Paris, Facult\u00e9 de M\u00e9decine, AP-HP-Centre Universit\u00e9 de Paris, H\u00f4pital Cochin, Service d\u2019Immunologie Biologique, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazib","family":"Pervaiz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"},{"name":"NUS Medicine Healthy Longevity Program, National University of Singapore, Singapore 117597, Singapore"},{"name":"Integrated Science and Engineering Program, NUS Graduate School, National University of Singapore, Singapore 117597, Singapore"},{"name":"NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"},{"name":"National University Cancer Institute, National University Health System, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.bbmt.2016.09.023","article-title":"The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease","volume":"23","author":"Cooke","year":"2017","journal-title":"Biol. 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