Hepatic irradiation persistently eliminates liver resident NK cells.
Hepatic irradiation persistently eliminates liver resident NK cells.
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DOI：
10.1371/journal.pone.0198904
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Ohdan H
中科院分区：
文献类型：
--
作者：
Nakano R;Ohira M;Yano T;Imaoka Y;Tanaka Y;Ohdan H
肝放射治疗肝胆恶性肿瘤常间接损伤肝组织，促进肝纤维化的发展。然而，很少有人知道肝脏照射对肝脏免疫系统，包括自然杀伤（NK）细胞的影响。因此，本研究的目的是探讨肝脏照射如何影响肝脏驻留NK细胞的功能和特性。建立了小鼠肝照射模型，用于检查肝照射对免疫细胞群和转移的特异性影响。该分析表明，肝脏照射减少了肝脏驻留NK细胞（DX 5-TRAIL+）的数量，但不影响肝脏或脾脏中的总NK数量或NK细胞的比例。这种效应与肝脏照射剂量有关。令人惊讶的是，肝脏居民NK人群在肝脏照射后两个月仍未恢复。我们还发现，肝照射限制了肝源性淋巴细胞对小鼠肝癌细胞系的细胞毒性作用，并促进了体内模型中的肝转移，尽管过继转移活化的NK细胞可以减轻转移性生长。最后，我们证明了肝脏照射破坏了肝脏驻留NK细胞的发育，即使在从骨髓，肝脏和脾脏过继转移前体细胞之后，这表明照射改变了肝脏的发育环境。总之，我们的数据表明，肝脏照射消除了DX 5-TRAIL+肝脏驻留NK细胞群，并抑制了肝脏中的抗肿瘤活性至少两个月。此外，肝脏照射阻止前体细胞分化为肝脏驻留的NK细胞。
Hepatic irradiation for the treatment of hepatobiliary malignancies often indirectly damages liver tissue and promotes the development of liver fibrosis. However, little is known concerning the effects of hepatic irradiation on the liver immune system, including natural killer (NK) cells. The aim of this study was therefore to investigate how hepatic irradiation influences the functions and characteristics of liver resident NK cells. An established murine hepatic irradiation model was used to examine the specific effects of hepatic irradiation on immune cell populations and metastasis. This analysis demonstrated that hepatic irradiation decreased the number of liver resident NK cells (DX5–TRAIL+), but did not affect the total NK number or proportions of NK cells in the liver or spleen. This effect was correlated with the hepatic irradiation dose. Surprisingly, the liver resident NK population had not recovered by two months after hepatic irradiation. We also found that hepatic irradiation limited the cytotoxic effects of liver-derived lymphocytes against a mouse hepatoma cell line and promoted hepatic metastases in an in vivo model, although adoptive transfer of activated NK cells could alleviate metastatic growth. Finally, we demonstrated that hepatic irradiation disrupted the development of liver-resident NK cells, even after the adoptive transfer of precursor cells from the bone marrow, liver, and spleen, suggesting that irradiation had altered the developmental environment of the liver. In summary, our data demonstrated that hepatic irradiation abolished the DX5–TRAIL+ liver-resident NK cell population and dampened antitumor activities in the liver for at least two months. Additionally, hepatic irradiation prevented differentiation of precursor cells into liver-resident NK cells.
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影响因子：
2
作者：
Imaeda M;Ishikawa H;Yoshida Y;Takahashi T;Ohkubo Y;Musha A;Komachi M;Nakazato Y;Nakano T
通讯作者：
Nakano T
肝脏驻留 NK 细胞和粘膜 ILC1 的差异表型和功能特性
影响因子：
12.8
作者：
Tang, Ling;Peng, Hui;Tian, Zhigang
通讯作者：
Tian, Zhigang
DOI：
10.4049/jimmunol.1302765
发表时间：
2014-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Crotta S;Gkioka A;Male V;Duarte JH;Davidson S;Nisoli I;Brady HJ;Wack A
通讯作者：
Wack A
影响因子：
15.9
作者：
Ohira, Masahiro;Ishiyama, Kohei;Ohdan, Hideki
通讯作者：
Ohdan, Hideki
影响因子：
51.1
作者：
Formenti, Silvia C.;Demaria, Sandra
通讯作者：
Demaria, Sandra