Fluvastatin-Pretreated Donor Cells Attenuated Murine aGVHD by Balancing Effector T Cell Distribution and Function under the Regulation of KLF2
Joint Authors
Pan, Bin
Zhao, Kai
Chen, Chong
Tian, Yu
Wang, Junjie
Yan, Zhiling
Zhu, Shengyun
Xu, Kailin
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-12-21
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Prevention of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still to be explored.
Statins are potent immunomodulatory agents that hold promise as novel and safe agents for aGVHD prophylaxis, yet the controversial effect and regulatory mechanism are incompletely understood.
Here, in an MHC mismatched murine model, we found that Fluvastatin-pretreated donor cells could attenuate aGVHD severity by remission tissue pathological injury.
Fluvastatin served to restrain effector T cells entry into aGVHD target organs from secondary lymphoid organs (SLOs).
The potential mechanism of correcting the effector T cell biased distribution was that Fluvastatin elevated CD62L and CCR7 expression while decreased CXCR3 and CD44 levels, which were correlated with Kruppel-like factor 2 (KLF2) sustention in donor-derived cells.
In addition, Fluvastatin was contributed to reducing cytokines IFN-γ, TNF-α, and granzyme-B production in allogeneic effector CD4+ and CD8+ T cells.
Furthermore, evidence confirmed that Fluvastatin had a long-lasting effect to sustain KLF2 expression both in vitro and in vivo even under the stimulated circumstance.
In conclusion, administration of Fluvastatin to donor mice showed protective effects against recipient aGVHD when compared to untreated mice due to the retention of effector T cells in lymphoid organs accompanying with reduction of nonlymphatic infiltration and related inflammatory cytokines.
American Psychological Association (APA)
Zhao, Kai& Tian, Yu& Wang, Junjie& Chen, Chong& Pan, Bin& Yan, Zhiling…[et al.]. 2020. Fluvastatin-Pretreated Donor Cells Attenuated Murine aGVHD by Balancing Effector T Cell Distribution and Function under the Regulation of KLF2. BioMed Research International،Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1137042
Modern Language Association (MLA)
Zhao, Kai…[et al.]. Fluvastatin-Pretreated Donor Cells Attenuated Murine aGVHD by Balancing Effector T Cell Distribution and Function under the Regulation of KLF2. BioMed Research International No. 2020 (2020), pp.1-17.
https://search.emarefa.net/detail/BIM-1137042
American Medical Association (AMA)
Zhao, Kai& Tian, Yu& Wang, Junjie& Chen, Chong& Pan, Bin& Yan, Zhiling…[et al.]. Fluvastatin-Pretreated Donor Cells Attenuated Murine aGVHD by Balancing Effector T Cell Distribution and Function under the Regulation of KLF2. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1137042
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1137042