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Under stimulation by inflammatory cytokines IFN\u2010\u03b3 and TNF\u2010\u03b1, human mesenchymal stromal cells (hMSCs) acquire a potent immunomodulatory function enabled by drastic induction of various effector genes, with some upregulated several magnitudes. However, whether the transcriptional upregulation of the immunomodulatory genes in hMSCs exposed to inflammatory cytokines is associated with genome\u2010wide nuclear reconfiguration has not been explored. Here, we demonstrate that hMSCs undergo remarkable nuclear reconfiguration characterized by an enlargement of the nucleus, downregulation of LMNB1 and LMNA\/C, decondensation of heterochromatin, and derepression of repetitive DNA. Interestingly, promyelocytic leukaemia\u2010nuclear bodies (PML\u2010NBs) were found to mediate the nuclear reconfiguration of hMSCs triggered by the inflammatory cytokines. Significantly, when PML was depleted, the immunomodulatory function of hMSCs conferred by cytokines was compromised, as reflected by the attenuated expression of effector molecules in hMSCs and their failure to block infiltration of immune cells to lipopolysaccharide (LPS)\u2010induced acute lung injury. Our results indicate that the immunomodulatory function of hMSCs conferred by inflammatory cytokines requires PML\u2010mediated chromatin loosening.<\/jats:p>","DOI":"10.1111\/cpr.13566","type":"journal-article","created":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T04:27:15Z","timestamp":1697862435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PML\u2010mediated nuclear loosening permits immunomodulation of mesenchymal stem\/stromal cells under inflammatory conditions"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0698-5216","authenticated-orcid":false,"given":"Yunpeng","family":"Chu","sequence":"first","affiliation":[{"name":"The Third Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine Soochow University Medical College  Suzhou 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