Leflunomide protects from T-cell-mediated liver injury in mice through inhibition of nuclear factor ?B

Hepatology ◽  
2004 ◽  
Vol 40 (5) ◽  
pp. 1160-1169 ◽  
Author(s):  
Motoaki Imose ◽  
Masahito Nagaki ◽  
Kiminori Kimura ◽  
Shinji Takai ◽  
Motohiro Imao ◽  
...  
Keyword(s):  
T Cell ◽  
Liver Injury ◽  
Nuclear Factor ◽  
Factor B

scholarly journals Pivotal role of nuclear factor ?B signaling in anti-CD40-induced liver injury in mice

Hepatology ◽  
2004 ◽  
Vol 40 (5) ◽  
pp. 1180-1189 ◽  
Author(s):  
Kiminori Kimura ◽  
Masahito Nagaki ◽  
Shinji Takai ◽  
Shinichi Satake ◽  
Hisataka Moriwaki
Keyword(s):  
Liver Injury ◽  
Pivotal Role ◽  
Nuclear Factor ◽  
Factor B

scholarly journals Mesenchymal stem cells alleviate experimental immune-mediated liver injury via chitinase 3-like protein 1-mediated T cell suppression

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Qiuli Liu ◽  
Xiaoyong Chen ◽  
Chang Liu ◽  
Lijie Pan ◽  
Xinmei Kang ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Liver Injury ◽  
T Cell Activation ◽  
Gene Set Enrichment Analysis ◽  
Human Umbilical Cord ◽  
Con A ◽  
Immune Mediated

AbstractLiver diseases with different pathogenesis share common pathways of immune-mediated injury. Chitinase-3-like protein 1 (CHI3L1) was induced in both acute and chronic liver injuries, and recent studies reported that it possesses an immunosuppressive ability. CHI3L1 was also expressed in mesenchymal stem cells (MSCs), thus we investigates the role of CHI3L1 in MSC-based therapy for immune-mediated liver injury here. We found that CHI3L1 was highly expressed in human umbilical cord MSCs (hUC-MSCs). Downregulating CHI3L1 mitigated the ability of hUC-MSCs to inhibit T cell activation, proliferation and inflammatory cytokine secretion in vitro. Using Concanavalin A (Con A)-induced liver injury mouse model, we found that silencing CHI3L1 significantly abrogated the hUC-MSCs-mediated alleviation of liver injury, accompanying by weakened suppressive effects on infiltration and activation of hepatic T cells, and secretion of pro-inflammatory cytokines. In addition, recombinant CHI3L1 (rCHI3L1) administration inhibited the proliferation and function of activated T cells, and alleviated the Con A-induced liver injury in mice. Mechanistically, gene set enrichment analysis showed that JAK/STAT signalling pathway was one of the most significantly enriched gene pathways in T cells co-cultured with hUC-MSCs with CHI3L1 knockdown, and further study revealed that CHI3L1 secreted by hUC-MSCs inhibited the STAT1/3 signalling in T cells by upregulating peroxisome proliferator-activated receptor δ (PPARδ). Collectively, our data showed that CHI3L1 was a novel MSC-secreted immunosuppressive factor and provided new insights into therapeutic treatment of immune-mediated liver injury.

scholarly journals Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment

2006 ◽  
Vol 103 (10) ◽  
pp. 3740-3745 ◽  
Author(s):  
T. So ◽  
J. Song ◽  
K. Sugie ◽  
A. Altman ◽  
M. Croft
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lineage Commitment ◽  
Nuclear Factor ◽  
Activated T Cells

scholarly journals Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury

Gut ◽  
1997 ◽  
Vol 41 (4) ◽  
pp. 534-540 ◽  
Author(s):  
V A J Maria ◽  
R M M Victorino
Keyword(s):  
T Cell ◽  
Liver Injury ◽  
Mononuclear Cells ◽  
Diagnostic Value ◽  
Drug Induced ◽  
Cell Reactivity ◽  
Peripheral Blood Mononuclear ◽  
Drug Induced Liver Injury ◽  
Prostaglandin Inhibitor ◽  
T Cell Reactivity

Background—Diagnosis of drug induced liver injury is usually based on a temporal relation between drug intake and clinical picture as well as on the exclusion of alternative causes. More precise diagnosis has been attempted by using in vitro specific T cell reactivity to drugs but the test has never reached general acceptability because of frequent negative results which could be explained, in part, by prostaglandin producing suppressor cells (PPSC).Aim—To analyse the diagnostic value of a modified test where lymphocyte responses to drugs are detected in the presence of a prostaglandin inhibitor.Patients—Ninety five patients with a clinical diagnosis of drug induced liver injury, 106 healthy controls, 35 individuals with recent exposure to the same drugs without adverse effects, and 15 patients with liver disease unrelated to drugs.Methods—Peripheral blood mononuclear cells (PBMC) were cultured in the presence of drugs alone and in the presence of drugs and a prostaglandin inhibitor. Responses were assessed by3H-thymidine incorporation in lymphocytes. Results were expressed as counts per minute and as stimulation indexes (SI).Results—When PBMC were stimulated with drugs alone, lymphocyte sensitisation to drugs (SI>2) was detected in 26% of the cases. This was noticeably increased (56%) when a prostaglandin inhibitor was added to the cultures. No reactivity was found in controls. In patients with possible sensitivity to several drugs, lymphocyte reactivity was detected to only one drug. The severity of the lesions, as assessed by aminotransferase concentrations and disease duration, was lower in patients with evidence of PPSC.Conclusions—This new approach is useful for the diagnosis of drug induced liver injury, particularly in patients exposed to more than one drug; furthermore, the presence of putative PPSC is associated with less severe forms of drug induced hepatitis.

scholarly journals Role of the Ca2+-Calcineurin-Nuclear Factor of Activated T cell Pathway in Mitofusin-2-Mediated Immune Function of Jurkat Cells

2018 ◽  
Vol 131 (3) ◽  
pp. 330-338 ◽  
Author(s):  
Xiu-Ping Xu ◽  
Yong-Ming Yao ◽  
Guang-Ju Zhao ◽  
Zong-Sheng Wu ◽  
Jun-Cong Li ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Function ◽  
Jurkat Cells ◽  
Nuclear Factor ◽  
Mitofusin 2 ◽  
Activated T Cell

scholarly journals PWE-281 Different effector T cell responses may account for different patterns of liver injury in childhood autoimmune liver disease

Gut ◽  
2012 ◽  
Vol 61 (Suppl 2) ◽  
pp. A412.1-A412 ◽  
Author(s):  
R Liberal ◽  
C Grant ◽  
G Mieli-Vergani ◽  
D Vergani ◽  
M Longhi
Keyword(s):  
Liver Disease ◽  
T Cell ◽  
Liver Injury ◽  
T Cell Responses ◽  
Autoimmune Liver Disease ◽  
Effector T Cell ◽  
Cell Responses
Sign in / Sign up

Export Citation Format

Share Document