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dc.contributor.authorMohammadpour, H.
dc.contributor.authorSarow, J.L.
dc.contributor.authorCao, X.
dc.date.accessioned2020-06-30T18:46:25Z
dc.date.available2020-06-30T18:46:25Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85086747266&doi=10.1172%2fjci.insight.137788&partnerID=40&md5=d38e356034ab5112f1ac056ec4e07d0d
dc.identifier.urihttp://hdl.handle.net/10713/13182
dc.description.abstractAcute graft versus host disease (aGvHD) remains a major impediment to successful allogeneic hematopoietic cell transplantation (allo-HCT). To solve this problem, a greater knowledge of factors that regulate the differentiation of donor T cells toward cytotoxic cells or Tregs is necessary. We report that the β2-adrenergic receptor (β2-AR) is critical for regulating this differentiation and that its manipulation can control aGvHD without impairing the graft-versus-tumor (GvT) effect. Donor T cell β2-AR expression and signaling is associated with decreased aGvHD when compared with recipients of β2-AR-/- donor T cells. We determined that β2-AR activation skewed CD4+ T cell differentiation in vitro and in vivo toward Tregs rather than the T helper 1 (Th1) phenotype. Treatment of allo-HCT recipients with a selective β2-agonist (bambuterol) ameliorated aGvHD severity. This was associated with increased Tregs, decreased cytotoxic T cells, and increased donor BM-derived myeloid-derived suppressor cells (MDSCs) in allogeneic and humanized xenogeneic aGvHD models. β2-AR signaling resulted in increased Treg generation through glycogen synthase kinase-3 activation. Bambuterol preserved the GvT effect by inducing NKG2D+ effector cells and central memory T cells. These data reveal how β-AR signaling can be targeted to ameliorate GvHD severity while preserving GvT effect.en_US
dc.description.urihttps://doi.org/10.1172/jci.insight.137788en_US
dc.language.isoen_USen_US
dc.publisherThe American Society for Clinical Investigationen_US
dc.relation.ispartofJCI insight
dc.subjectBone marrow transplantationen_US
dc.subjectImmunologyen_US
dc.subjectTransplantationen_US
dc.titleβ2-Adrenergic receptor activation on donor cells ameliorates acute GvHDen_US
dc.typeArticleen_US
dc.identifier.doi10.1172/jci.insight.137788
dc.identifier.pmid32437333


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