Inflammatory Regulation by TLR3 in Acute Hepatitis
| Autor: | Xiaoyan Xiao, Daniel Rodriguez-Pinto, Dake Qi, Richard A. Flavell, Peng Zhao, F. Susan Wong, Li Wen, Lena Alexopoulou, Octavian Henegariu |
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| Přispěvatelé: | Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, Department of Cardiology, Shandong Provincial Hospital, Shandong University, Section of Cardiovascular Medicine, Department of Internal Medicine, Howard Hughes Medical Institute and Department of Immunobiology, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Department of Cellular and Molecular Medicine [Bristol], University of Bristol [Bristol], Yale School of Medicine [New Haven, Connecticut] (YSM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Inflammation
viruses Immunology chemical and pharmacologic phenomena Inflammation MESH: Concanavalin A Biology Peripheral blood mononuclear cell MESH: Hematopoietic Stem Cells MESH: Hepatocytes 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy MESH: Animals MESH: Mice 030304 developmental biology Hepatitis 0303 health sciences virus diseases hemic and immune systems MESH: Toll-Like Receptor 3 MESH: Hepatitis Toxic medicine.disease MESH: Gene Expression Regulation 3. Good health Haematopoiesis MESH: T-Lymphocytes medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis Hepatocyte TLR3 Cancer research MESH: Acute Disease [SDV.IMM]Life Sciences [q-bio]/Immunology Bone marrow medicine.symptom MESH: Liver |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 183 (6), pp.3712-9. ⟨10.4049/jimmunol.0901221⟩ Journal of Immunology, 2009, 183 (6), pp.3712-9. ⟨10.4049/jimmunol.0901221⟩ |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0901221 |
| Popis: | TLR3 is known to respond to dsRNA from viruses, apoptotic cells, and/or necrotic cells. Dying cells are a rich source of ligands that can activate TLRs, such as TLR3. TLR3 expressed in the liver is likely to be a mediator of innate activation and inflammation in the liver. The importance of this function of TLR3 during acute hepatitis has not previously been fully explored. We used the mouse model of Con A-induced hepatitis and observed a novel role for TLR3 in hepatocyte damage in the absence of an exogenous viral stimulus. Interestingly, TLR3 expression in liver mononuclear cells and sinus endothelial cells was up-regulated after Con A injection and TLR3−/− mice were protected from Con A-induced hepatitis. Moreover, splenocytes from TLR3−/− mice proliferated less to Con A stimulation in the presence of RNA derived from damaged liver tissue compared with wild-type (WT) mice. To determine the relative contribution of TLR3 expression by hematopoietic cells or nonhematopoietic to liver damage during Con A-induced hepatitis, we generated bone marrow chimeric mice. TLR3−/− mice engrafted with WT hematopoietic cells were protected in a similar manner to WT mice reconstituted with TLR3−/− bone marrow, indicating that TLR3 signaling in both nonhematopoietic and hematopoietic cells plays an important role in mediating liver damage. In summary, our data suggest that TLR3 signaling is necessary for Con A-induced liver damage in vivo and that TLR3 regulates inflammation and the adaptive T cell immune response in the absence of viral infection. |
| Databáze: | OpenAIRE |
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