期刊
BONE MARROW TRANSPLANTATION
卷 56, 期 11, 页码 2672-2681出版社
SPRINGERNATURE
DOI: 10.1038/s41409-021-01363-1
关键词
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资金
- National Fund for Scientific Research (FNRS) [T.0069.15, T.0016.20]
- Belgian Fondation contre le cancer [FAF-C/2016/889]
- Leon Fredericq fund
- Anti-Cancer Center at the University of Liege
The study found that itacitinib can reduce the engraftment of human T cells, increase the frequency of regulatory T cells, and alleviate xGVHD in NSG mice transplanted with hPBMC.
We assessed the impact of the Janus Kinase (JAK) 1 inhibitor itacitinib on xenogeneic graft-versus-host disease (xGVHD). XGVHD was induced by i.v. injection 20 x 10(6) human peripheral blood mononuclear cells (hPBMC) in NSG mice on day 0. Itacitinib (3 mg, approximate to 120 mg/kg) or methylcellulose was administered by force-feeding twice a day from day 3 to day 28. Mice were followed for xGVHD score and survival. In addition, human T-cell engraftment and as well as human T-cell subtypes were monitored in blood on days 14, 21, and 28 after transplantation. We observed that itacitinib-treated mice had significantly longer survival than control mice (median 45 versus 33 days; P < 0.001). Further, they also had lower absolute numbers of human CD4(+) T cells on days 21 and 28 after transplantation as well as of human CD8(+) T cells on days 14, 21, and 28 after transplantation. In addition, itacitinib-treated mice had higher frequencies of human regulatory T cells (Treg) on days 21 and 28 after transplantation. In summary, our data indicate that itacitinib decreases human T-cell engraftment, increases Treg frequencies and attenuates xGVHD in NSG mice transplanted with hPBMC.
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