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Publication : Exacerbation of pathogenic Th17-cell-mediated cutaneous graft-versus-host-disease in human IL-1β and IL-23 transgenic humanized mice.

First Author  Ito R Year  2019
Journal  Biochem Biophys Res Commun Volume  516
Issue  2 Pages  480-485
PubMed ID  31230747 Mgi Jnum  J:291209
Mgi Id  MGI:6442981 Doi  10.1016/j.bbrc.2019.06.094
Citation  Ito R, et al. (2019) Exacerbation of pathogenic Th17-cell-mediated cutaneous graft-versus-host-disease in human IL-1beta and IL-23 transgenic humanized mice. Biochem Biophys Res Commun 516(2):480-485
abstractText  Although Th17cells are closely linked to cutaneous graft-versus-host-disease (GVHD) in mouse models, this association remains unclear in human GVHD. In this study, we established a novel xenogeneic cutaneous GVHD model using humanized mice. To induce the differentiation of human Th17cells, we created transgenic NOG mice expressing human IL-1beta and IL-23 cytokines (hIL-1beta/23Tg) and transplanted with human CD4(+) T cells. The pathologies of cutaneous GVHD, such as a decrease in body weight, alopecia, and T cell inflammation in the skin, were observed much earlier in hIL-1beta/23Tg mice compared with non-Tg mice after human CD4(+) T cell transplantation. In the skin of Tg mice, IL-17- and IFNgamma-producing pathogenic Th17cells were significantly accumulated. Furthermore, high infiltration of murine neutrophils was seen in the skin of Tg mice, but not non-Tg mice, which may have been the cause of the severe alopecia. CD4(+) T-cell-transferred hIL-1beta/23Tg mice were therefore highly sensitive models for inducing cutaneous GVHD mediated by human pathogenic Th17cells.
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