Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the cell growth of Langerhans cell histiocytosis.
Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the cell growth of Langerhans cell histiocytosis.
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DOI：
10.18632/oncotarget.16936
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发表时间：
2017-06-06
期刊：
影响因子：
--
通讯作者：
Haga H
中科院分区：
文献类型：
--
作者：
Takei Y;Ueshima C;Kataoka TR;Hirata M;Sugimoto A;Rokutan-Kurata M;Moriyoshi K;Ono K;Murakami I;Iwamoto S;Haga H
杀伤细胞免疫球蛋白样受体(KIR)2DL4(CD158d)是人类白细胞抗原G的受体。KIR2DL4在人类自然杀伤细胞淋巴瘤和肥大细胞增生症中的作用已有报道，但在朗格汉斯细胞组织细胞增生症(LCH)中未见报道。在此，我们检测了KIR2DL4在LCH中的表达和功能。病理标本中，KIR2DL4免疫组织化学阳性27例(75.0%)。其表达与年龄、性别、部位、多系统或单系统、BRAFV600E免疫染色状态无关。我们还证实了KIR2DL4在人LCH样细胞系ELD-1和PRU-1中的表达。KIR2DL4蛋白主要分布于ELD-1细胞的胞膜和胞浆中，而在PRU-1细胞中仅分布于胞浆中。KIR2DL4激动型抗体可抑制细胞外信号调节蛋白激酶(ERKs)的磷酸化，抑制细胞生长，抑制细胞生长，但对PRU-1细胞无影响。这些结果表明，KIR2DL4介导的ERK抑制可能是LCH细胞的治疗靶点。
Killer cell immunoglobulin-like receptor (KIR) 2DL4 (CD158d) is a receptor for human leukocyte antigen-G. The function of KIR2DL4 has been reported in human natural killer cell lymphoma and mastocytosis, but not in Langerhans cell histiocytosis (LCH). Herein, we examined the expression and function of KIR2DL4 in LCHs. In pathological specimens, 27 of 36 LCH cases (75.0%) were immunohistochemically positive for KIR2DL4. Its expression was independent of age, gender, location, multi- or single-system, and the status of BRAFV600E immunostaining. We also confirmed the expression of KIR2DL4 mRNA and protein in the human LCH-like cell lines ELD-1 and PRU-1. KIR2DL4 protein was distributed in the membrane and cytoplasm of ELD-1 cells, but only in the cytoplasm of PRU-1 cells. An agonistic antibody against KIR2DL4 reduced phosphorylation of extracellular signal-regulated kinases (ERKs) and suppressed the cell growth of ELD-1 cells in a Src homology region 2 domain-containing phosphatase-2 dependent manner, but it had no effect in PRU-1 cells. These results suggest that KIR2DL4-mediated ERK suppression is a possible therapeutic target for LCH cells.
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DOI：
10.1084/jem.20130977
发表时间：
2014-04-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Berres ML;Lim KP;Peters T;Price J;Takizawa H;Salmon H;Idoyaga J;Ruzo A;Lupo PJ;Hicks MJ;Shih A;Simko SJ;Abhyankar H;Chakraborty R;Leboeuf M;Beltrão M;Lira SA;Heym KM;Bigley V;Collin M;Manz MG;McClain K;Merad M;Allen CE
通讯作者：
Allen CE
影响因子：
20.3
作者：
Sahm, Felix;Capper, David;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
4.4
作者：
Rajagopalan, S;Fu, J;Long, EO
通讯作者：
Long, EO
影响因子：
6
作者：
Kucuk, Can;Hu, Xiaozhou;Chan, Wing C.
通讯作者：
Chan, Wing C.
影响因子：
4.8
作者：
Favata, MF;Horiuchi, KY;Trzaskos, JM
通讯作者：
Trzaskos, JM