Nrf2 regulates CD4(+) T cell-induced acute graft-versus-host disease in mice Journal Article

Authors: Tsai, J. J.; Velardi, E.; Shono, Y.; Argyropoulos, K. V.; Holland, A. M.; Smith, O. M.; Yim, N. L.; Rao, U. K.; Kreines, F. M.; Lieberman, S. R.; Young, L. F.; Lazrak, A.; Youssef, S.; Fu, Y. Y.; Liu, C.; Lezcano, C.; Murphy, G. F.; Na, I. K.; Jenq, R. R.; Hanash, A. M.; Dudakov, J. A.; van den Brink, M. R. M.
Article Title: Nrf2 regulates CD4(+) T cell-induced acute graft-versus-host disease in mice
Abstract: Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a ubiquitously expressed transcription factor that is well known for its role in regulating the cellular redox pathway. Although there is mounting evidence suggesting a critical role for Nrf2 in hematopoietic stem cells and innate leukocytes, little is known about its involvement in T-cell biology. In this study, we identified a novel role for Nrf2 in regulating alloreactive T-cell function during allogeneic hematopoietic cell transplantation (allo-HCT). We observed increased expression and nuclear translocation of Nrf2 upon T-cell activation in vitro, especially in CD41 donor T cells after allo-HCT. Allo-HCT recipients of Nrf22/2 donor T cells had significantly less acute graft-versus-host disease (GVHD)-induced mortality, morbidity, and pathology. This reduction in GVHD was associated with the persistence of Helios1 donor regulatory T cells in the allograft, as well as defective upregulation of the gut-homing receptor LPAM-1 on alloreactive CD81 T cells. Additionally, Nrf22/2 donor CD81 T cells demonstrated intact cytotoxicity against allogeneic target cells. Tumor-bearing allo-HCT recipients of Nrf22/2 donor T cells had overall improved survival as a result of preserved graft-versus-tumor activity and reduced GVHD activity. Our findings characterized a previously unrecognized role for Nrf2 in T-cell function, as well as revealed a novel therapeutic target to improve the outcomes of allo-HCT. © 2018 by The American Society of Hematology; all rights reserved.
Journal Title: Blood
Volume: 132
Issue: 26
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2018-12-27
Start Page: 2763
End Page: 2774
Language: English
DOI: 10.1182/blood-2017-10-812941
PUBMED: 30381375
PROVIDER: scopus
PMCID: PMC6307985
Notes: Article -- Export Date: 1 February 2019 -- Source: Scopus
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MSK Authors
  1. Il-Kang Na
    24 Na
  2. Alan M Hanash
    81 Hanash
  3. Jarrod Andrew Dudakov
    58 Dudakov
  4. Robert R Jenq
    100 Jenq
  5. Jennifer Tsai
    44 Tsai
  6. Yusuke Shono
    33 Shono
  7. Enrico Velardi
    44 Velardi
  8. Odette Marsinay Smith
    95 Smith
  9. Uttam Keshav Rao
    28 Rao
  10. Nury Yim
    25 Yim
  11. Amanda M Holland
    52 Holland
  12. Lauren Young
    39 Young
  13. Fabiana Maria Kreines
    14 Kreines
  14. Ya-Yuan   Fu
    5 Fu
  15. Amina Lazrak
    13 Lazrak