Ischemic Injury Enhances Dendritic Cell Immunogenicity via TLR4 and NF-κB Activation
| Autor: | Kambiz Zandi-Nejad, Mollie Jurewicz, Said Movahedi Naini, Andrea Augello, Reza Abdi, Takaharu Ichimura, Ayumi Takakura |
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| Rok vydání: | 2010 |
| Předmět: |
inorganic chemicals
T-Lymphocytes T cell Immunology Ischemia Mice Transgenic chemical and pharmacologic phenomena Ligands Lymphocyte Activation digestive system Mice medicine Animals Mineral Oil Immunology and Allergy Cells Cultured Mice Knockout Mice Inbred BALB C business.industry Immunogenicity fungi NF-kappa B Dendritic Cells Dendritic cell medicine.disease Coculture Techniques Toll-Like Receptor 2 Up-Regulation Hsp70 Mice Inbred C57BL Toll-Like Receptor 4 Transplantation medicine.anatomical_structure Apoptosis TLR4 business Injections Intraperitoneal |
| Zdroj: | The Journal of Immunology. 184:2939-2948 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0901889 |
| Popis: | Ischemic (isc) injury during the course of transplantation enhances the immunogenicity of allografts and thus results in poorer graft outcome. Given the central role of dendritic cells (DCs) in mounting alloimmune responses, activation of donor DCs by ischemia may have a primary function in the increased immunogenicity of isc allografts. In this study, we sought to investigate the effect of ischemia on DC activity in vitro. Following induction of ischemia, bone marrow-derived DCs were shown to augment allogeneic T cell proliferation as well as the IFN-γ response. Isc DCs produced greater levels of IL-6, and isc insult was concurrent with NF-κB activation. TLR4 ligation was also shown to occur in isc DCs, most likely in response to the endogenous ligand heat shock protein 70, which was found to be elevated in DCs following isc injury, and lack of TLR4 abrogated the observed effects of isc DCs. As compared with control DCs, isc DCs injected into the footpads of mice demonstrated enhanced migration, which was concomitant with increased recipient T cell activity. Moreover, isc DCs underwent a greater degree of apoptosis in the lymph nodes of injected mice, which may further demonstrate enhanced immunogenicity of isc DCs. We thus show that isc injury of DCs enhances DC function, augments the allogeneic T cell response, and occurs via ligation of TLR4, followed by activation of NF-κB. These data may serve to identify novel therapeutic targets to attenuate graft immunogenicity following ischemia. |
| Databáze: | OpenAIRE |
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