Disruption of TIM-4 in dendritic cell ameliorates hepatic warm IR injury through the induction of regulatory T cells
| Autor: | Ji Li, Xiao-liang Liu, Xin Zhao, Huanqiu Liu |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adoptive cell transfer
T cell Primary Cell Culture Immunology Cell Separation Biology T-Lymphocytes Regulatory Mice Th2 Cells Liver Function Tests medicine Animals IL-2 receptor Antigen-presenting cell Molecular Biology Liver injury Interleukin-2 Receptor alpha Subunit Temperature Antibodies Monoclonal Membrane Proteins FOXP3 Forkhead Transcription Factors Dendritic Cells Dendritic cell medicine.disease Adoptive Transfer Coculture Techniques Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Liver Reperfusion Injury CD4 Antigens Cancer research Cytokine secretion Interleukin-4 STAT6 Transcription Factor Signal Transduction |
| Zdroj: | Molecular Immunology. 66:117-125 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2015.02.004 |
| Popis: | Hepatic ischaemia reperfusion (IR) injury results from the infiltration of multiple immune cells especially dendritic cells (DC). T-cell immunoglobulin-domain and mucin-domain 4 (TIM-4) is a type I cell-surface glycoprotein which is extensively expressed on antigen presenting cells (APC) like DC and macrophages. TIM-4 has been demonstrated to be implicated in mucosal allergy, skin allograft rejection and tumour-immune tolerance. However, the role of TIM-4 expressed on DC in hepatic IR injury remains largely unknown. In the present study, we aimed to investigate whether and how DC expressed TIM-4 was involved in hepatic IR injury. With segmental hepatic warm ischaemia mice models, we demonstrated that promoted DC infiltration and increased TIM-4 expression were induced by hepatic IR. Blockade of TIM-4 by anti-TIM-4 mAb (0.35mg/mouse) markedly ameliorated hepatic injury and reduced inflammatory cytokine secretion. Furthermore, in a DC:CD4+ T cell co-culture system, blockade of TIM-4 on DC significantly inhibited T helper-2 cell differentiation and facilitated induced CD4+ CD25+ Foxp3+ T regulatory cell (iTreg) expansion. Interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (Stat 6) signalling was shown to be impeded by TIM-4 blockade and involved in iTreg generation. Additionally, adoptive transfer of iTreg produced by TIM-4 blockade into hepatic IR mice models remarkably attenuated liver injury. We conclude that TIM-4 on DC play a critical role in hepatic IR injury and may be an efficient target for the prevention of liver or other organ IR injury. |
| Databáze: | OpenAIRE |
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