Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes.

Frontiers in transplantation Pub Date : 2024-12-11 eCollection Date: 2024-01-01 DOI:10.3389/frtra.2024.1448650

Ke Zeng, Hongbing Ma, Meixian Huang, Mi-Ae Lyu, Tara Sadeghi, Christopher R Flowers, Simrit Parmar

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Abstract

Background: Adoptive therapy with umbilical cord blood (UCB) T-regulatory (Treg) cells can prevent graft vs. host disease (GVHD). We hypothesize that UCB Tregs can treat GVHD and synergize with ruxolitinib, Jak2 inhibitor, to improve outcomes.

Methods: UCB Treg potency and efficacy was examined using cell suppression assay and xenogeneic GVHD model, respectively. Ruxolitinib was fed continuously in presence or absence of CellTraceViolet tagged UCB Tregs on days +4, +7, +11, +18. Mice were followed for survival, GVHD score, hematology parameters and inflammation.

Results: Addition of ruxolitinib to UCB Tregs exerted synergistic suppressor function in vitro and improved persistence of UCB Tregs in vivo. Lower GVHD score, improved survival, increased hemoglobin level and platelet count, decreased inflammatory cytokines and decrease in CD3⁺ T cell lung infiltrate was observed in UCB Tregs+ruxolitinib recipients.

Conclusion: UCB Treg+Ruxolitinib combination improves outcomes in xenogeneic GVHD and should be explored in a clinical setting.

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脐带血T调节细胞与ruxolitinib协同作用改善GVHD结果。

背景：脐带血（UCB） t调节（Treg）细胞过继治疗可以预防移植物抗宿主病（GVHD）。我们假设UCB Tregs可以治疗GVHD，并与Jak2抑制剂ruxolitinib协同，以改善结果。方法：采用细胞抑制法和异种GVHD模型分别检测UCB的Treg效价和疗效。在+4、+7、+11、+18天连续喂食Ruxolitinib，无论是否存在CellTraceViolet标记的UCB treg。随访小鼠的生存、GVHD评分、血液学参数和炎症。结果：ruxolitinib加入UCB Tregs具有协同抑制作用，提高了UCB Tregs在体内的持久性。UCB Tregs+ruxolitinib受体GVHD评分降低，生存率提高，血红蛋白水平和血小板计数升高，炎症因子减少，CD3+ T细胞肺浸润减少。结论：UCB Treg+Ruxolitinib联合治疗可改善异种GVHD的预后，值得在临床环境中进行探索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Frontiers in transplantation

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