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Galectin\u20109 negatively regulates CD4 effector T cell (Th1 and Th17) function by binding to Tim\u20103. However, the relationship between Galectin\u20109\/Tim\u20103 and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T subsets in patients with aGVHD after Haplo\u2010HSCT (haploidentical peripheral blood hematopoietic stem cell transplantation) has not been fully elucidated. Here, we investigated the role of Galectin\u20109 and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T subsets in aGVHD after haplo\u2010HSCT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty\u2010two patients underwent Haplo\u2010HSCT (26 without aGVHD and 16 with aGVHD), and 20 healthy controls were included. The concentrations of Galectin\u20109, interferon\u2010gamma (IFN\u2010\u03b3), interleukin (IL)\u20104, transforming growth factor (TGF)\u2010\u03b2, and IL\u201017 in the serum and culture supernatant were measured using enzyme\u2010linked immunosorbent assay or cytometric bead array. The expression levels of Galectin\u20109, PI3K, p\u2010PI3K, and p\u2010mTOR protein were detected by western blot analysis. Flow cytometry was used to analyze the proportions of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell subsets. Bioinformatics analysis was performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In patients with aGVHD, regulatory T (Treg) cells and Galectin\u20109 decreased, and the Th1, Th17, and Treg cells were significantly imbalanced. Moreover, Treg and Galectin\u20109 were rapidly reconstituted in the early stage of patients without aGVHD after Haplo\u2010HSCT, but Th17 cells were reconstituted slowly. Furthermore, Tim\u20103 upregulation on Th17 and Th1 cells was associated with excessive activation of the PI3K\/AKT pathway in patients with aGVHD. Specifically, in vitro treatment with Galectin\u20109 reduced IFN\u2010\u03b3 and IL\u201017 production while augmenting TGF\u2010\u03b2 secretion. Bioinformatics analysis suggested the potential involvement of the PI3K\/AKT\/mTOR pathway in aGVHD. Mechanistically, exogenous Galectin\u20109 was found to mitigate aGVHD by restoring the Treg\/Teffs (effector T cells) balance and suppressing PI3K.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Galectin\u20109 may ameliorate aGVHD after haplo\u2010HSCT by modulating Treg\/Teffs balance and regulating the PI3K\/AKT\/mTOR pathway. Targeting Galectin\u20109 may hold potential value for the treatment of aGVHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.1177","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T06:59:21Z","timestamp":1707893961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Galectin\u20109 alleviates acute graft\u2010versus\u2010host disease after haplo\u2010hematopoietic stem cell transplantation by regulating regulatory T cell\/effector T cell imbalance"],"prefix":"10.1002","volume":"12","author":[{"given":"Nannan","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Shihezi University Shihezi 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