Ma Wen-Tao, Jia Yan-Jie, Liu Qing-Zhi, Yang Yan-Qing, Yang Jing-Bo, Zhao Zhi-Bin, Yang Zhen-Ye, Shi Qing-Hua, Ma Hong-Di, Gershwin M Eric, Lian Zhe-Xiong
Liver Immunology Laboratory, Institute of Immunology, Hefei, China.
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Cell Death Dis. 2017 May 25;8(5):e2827. doi: 10.1038/cddis.2017.47.
Molecular mechanisms that modulate liver regeneration are of critical importance for a number of hepatic disorders. Kupffer cells and natural killer (NK) cells are two cell subsets indispensable for liver regeneration. We have focused on these two populations and, in particular, the interplay between them. Importantly, we demonstrate that deletion of the myeloid phosphatase and tensin homolog on chromosome 10 (PTEN) leading to an M2-like polarization of Kupffer cells, which results in decreased activation of NK cells. In addition, PTEN-deficient Kupffer cells secrete additional factors that facilitate the proliferation of hepatocytes. In conclusion, PTEN is critical for inhibiting M2-like polarization of Kupffer cells after partial hepatectomy, resulting in NK cell activation and thus the inhibition of liver regeneration. Furthermore, PTEN reduces growth factor secretion by Kupffer cells. Our results suggest that targeting PTEN on Kupffer cells may be useful in altering liver regeneration in patients undergoing liver resection.
调节肝脏再生的分子机制对多种肝脏疾病至关重要。库普弗细胞和自然杀伤（NK）细胞是肝脏再生不可或缺的两个细胞亚群。我们专注于这两个细胞群体，特别是它们之间的相互作用。重要的是，我们证明10号染色体上的髓样磷酸酶和张力蛋白同源物（PTEN）缺失会导致库普弗细胞向M2样极化，从而导致NK细胞活化降低。此外，PTEN缺陷的库普弗细胞分泌促进肝细胞增殖的其他因子。总之，PTEN对于抑制部分肝切除术后库普弗细胞的M2样极化至关重要，从而导致NK细胞活化，进而抑制肝脏再生。此外，PTEN减少库普弗细胞生长因子的分泌。我们的结果表明，靶向库普弗细胞上的PTEN可能有助于改变肝切除患者的肝脏再生。
