TNF-α is essential in the induction of fatal autoimmune hepatitis in mice through upregulation of hepatic CCL20 expression

Autor: Satoru Iwamoto, Hisayo Nishiura, Masahiro Kido, Ryutaro Maruoka, Tsutomu Chiba, Taku Okazaki, Nobuhiro Aoki, Norihiko Watanabe, Aki Ikeda
Rok vydání: 2013
Předmět:
T-Lymphocytes
medicine.medical_treatment
Programmed Cell Death 1 Receptor
Gene Expression
Stimulation
Kaplan-Meier Estimate
Autoimmune hepatitis
Lymphocyte Activation
Mice
Cell Movement
immune system diseases
Immunology and Allergy
Medicine
Cells
Cultured
Mice
Knockout
Mice
Inbred BALB C
biology
Reverse Transcriptase Polymerase Chain Reaction
Antibodies
Monoclonal
hemic and immune systems
Flow Cytometry
Thymectomy
Up-Regulation
Survival Rate
Hepatitis
Autoimmune
Liver
Tumor necrosis factor alpha
Antibody
Immunology
Enzyme-Linked Immunosorbent Assay
chemical and pharmacologic phenomena
Mouse model
Downregulation and upregulation
Animals
Hepatitis
Chemokine CCL20
Tumor Necrosis Factor-alpha
business.industry
medicine.disease
Antibodies
Neutralizing
digestive system diseases
TNF-α antagonist
CCL20
TNF-α
Hepatocytes
biology.protein
business
Spleen
Zdroj: Clinical Immunology. 146:15-25
ISSN: 1521-6616
Popis: It is unclear what roles TNF-α has in the development of autoimmune hepatitis (AIH) and whether AIH is responsive to anti-TNF-α. We recently developed a mouse model of fatal AIH that develops in PD-1-deficient mice thymectomized three days after birth, finding that CCR6-CCL20 axis-dependent migration of dysregulated splenic T cells is crucial to induce AIH. In this study, we show the indispensable role of TNF-α in the development of AIH. Administering anti-TNF-α prevented the induction, but treatment by anti-TNF-α after the induction did not suppress progression. Administering anti-TNF-α did not prevent splenic T-cell activation, but did suppress hepatic CCL20 expression. In contrast, administering anti-CCL20 suppressed AIH but not elevated serum TNF-α levels. TNF-α stimulation enhanced CCL20 expression in hepatocytes. These findings suggest that TNF-α is essential in the induction of AIH through upregulation of hepatic CCL20 expression, which allows migration of dysregulated splenic T cells.
Databáze: OpenAIRE
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