Hepatocyte DAX1 deletion exacerbates inflammatory liver injury by inducing the recruitment of CD4+ and CD8+ T cells through NF-κB p65 signaling pathway in mice

Cited 0 time in scopus
Metadata Downloads
Title
Hepatocyte DAX1 deletion exacerbates inflammatory liver injury by inducing the recruitment of CD4+ and CD8+ T cells through NF-κB p65 signaling pathway in mice
Author(s)
Hyo Jeong Yun; Young Joo Suh; Yu-Bin Kim; Eun Jung Kang; Jung-Hyeon ChoiYoung Keun ChoiIn-Bok LeeDong Hee ChoiYun Jeong SeoJung Ran Noh; H S Choi; Yong-Hoon KimChul-Ho Lee
Bibliographic Citation
International Journal of Molecular Sciences, vol. 23, no. 22, pp. 14009-14009
Publication Year
2022
Abstract
Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; NR0B1) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA). C57BL/6J (WT), myeloid cell-specific Dax1 knockout (MKO), and hepatocyte-specific Dax1 knockout (LKO) mice received single intravenous administration of ConA. Histopathological changes in liver and plasma alanine aminotransferase and aspartate aminotransferase levels in Dax1 MKO mice were comparable with those in WT mice following ConA administration. Unlike Dax1 MKO mice, Dax1 LKO mice were greatly susceptible to ConA-induced liver injury, which was accompanied by enhanced infiltration of immune cells, particularly CD4+ and CD8+ T cells, in the liver. Factors related to T-cell recruitment, including chemokines and adhesion molecules, significantly increased following enhanced and prolonged phosphorylation of NF-κB p65 in the liver of ConA-administered Dax1 LKO mice. This is the first study to demonstrate that hepatocyte-specific DAX1 deficiency exacerbates inflammatory liver injury via NF-κB p65 activation, thereby causing T-cell infiltration by modulating inflammatory chemokines and adhesion molecules. Our results suggest DAX1 as a therapeutic target for fulminant hepatitis treatment.
Keyword
Cncanavalin ADAX1Inflammatory liver injuryNF-kBT cell
ISSN
1661-6596
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms232214009
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.