Autoimmune hepatitis induction can occur in the liver
Autoimmune hepatitis induction can occur in the liver
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DOI：
10.1111/liv.14296
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发表时间：
2019-12-01
影响因子：
6.7
通讯作者：
Hardtke-Wolenski, Matthias
中科院分区：
文献类型：
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作者：
Dywicki, Janine;Buitrago-Molina, Laura Elisa;Hardtke-Wolenski, Matthias
肝脏中T细胞的启动被广泛接受。尽管如此，自身免疫性肝炎（AIH）的免疫激活是否发生在肝脏或脾脏仍存在争议。为了解决这个问题，我们切除小鼠脾脏，并诱导实验小鼠AIH（emAIH）与腺病毒（Ad）表达甲酰亚胺转移酶环脱氨酶（FTCD）。脾切除术后，实验小鼠比对照小鼠发展更高程度的emAIH。此外，脾切除小鼠窝藏更多的肝内B细胞和不成比例的少量调节性T细胞（T细胞）内减少的T细胞群在炎症部位。这些结果提示脾不是AIH的诱发部位。相比之下，脾脏似乎具有保护功能，因为切除脾脏的动物的病理评分更严重。这些发现对AIH的病因学有重要意义。
The priming of T cells in the liver is widely accepted. Nonetheless, it is controversial whether immune activation in autoimmune hepatitis (AIH) occurs in the liver or in the spleen. To address this issue, we splenectomized mice and induced experimental murine AIH (emAIH) with an adenovirus (Ad)-expressing formiminotransferase cyclodeaminase (FTCD). Post-splenectomy, the experimental mice developed emAIH to a higher extent than the control mice. In addition, splenectomized mice harboured more intrahepatic B cells and a disproportionately small number of regulatory T cells (Tregs) within a reduced T cell population at the site of inflammation. These results imply that the spleen is not the site of AIH induction. In contrast, the spleen seems to have a protective function since the pathological score was more severe in splenectomized animals. These findings have important implications for the aetiology of AIH.