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However, the relationship between macrophage polarization imbalance and functional defects in BMSCs, as well as the involvement of associated molecules in BMSCs' defects, is not well understood. This study aimed to investigate the regulatory effects of high mobility group protein 1 (HMGB1) on the physiological functions of BMSCs, specifically in relation to macrophage polarization imbalance. Patients with ITP showed dysregulation in monocyte\/macrophage polarization and impaired BMSCs function. HMGB1 was found to have a negative impact on the ability of BMSCs to regulate the imbalance in macrophage polarization, especially when inflammatory factors are present. The MyD88\u2010dependent pathway downstream of BMSCs was found to be significantly enhanced with HMGB1 treatment. Furthermore, treatment with toll\u2010like receptor 4 (TLR4) inhibitors successfully restored the regulatory capacity of BMSCs in ameliorating macrophage polarization imbalance and effectively inhibited the activation of the MyD88\u2010dependent pathway. Meanwhile, infusion of si\u2010TLR4\u2010BMSCs reversed HMGB1\u2010induced platelet dysfunction and reduced over\u2010polarization to M1\u2010like macrophages in the ITP mouse model. Consequently, targeting the HMGB1\u2010TLR4 pathway could be a potential approach to restore the immunoregulatory function of BMSCs.<\/jats:p>","DOI":"10.1111\/bjh.19709","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T23:49:40Z","timestamp":1724284180000},"page":"1516-1531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Activation of the <scp>HMGB1<\/scp>\u2010<scp>TLR4<\/scp> pathway impacts the functionality of bone marrow mesenchymal stem cells and disrupts macrophage polarization in immune thrombocytopenia"],"prefix":"10.1111","volume":"205","author":[{"given":"Ziyang","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Hematology Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat\u2010Sen Memorial Hospital, Sun 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