Oncotarget

Research Papers: Pathology:

Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the cell growth of Langerhans cell histiocytosis

Yusuke Takei, Chiyuki Ueshima, Tatsuki R. Kataoka _, Masahiro Hirata, Akihiko Sugimoto, Mariyo Rokutan-Kurata, Koki Moriyoshi, Kazuo Ono, Ichiro Murakami, Sanju Iwamoto and Hironori Haga

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:36964-36972. https://doi.org/10.18632/oncotarget.16936

Metrics: PDF 2263 views  |   HTML 2264 views  |   ?  


Abstract

Yusuke Takei1,*, Chiyuki Ueshima1,*, Tatsuki R. Kataoka1,*, Masahiro Hirata1, Akihiko Sugimoto1, Mariyo Rokutan-Kurata1, Koki Moriyoshi1,2, Kazuo Ono3, Ichiro Murakami4, Sanju Iwamoto5 and Hironori Haga1

1 Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan

2 Department of Diagnostic Pathology, Kyoto Medical Center, Kyoto, Japan

3 Department of Pathology, Japan Red Cross Society Wakayama Medical Center, Wakayama, Japan

4 Department of Pathology, School of Medicine, Kochi University Faculty of Medicine, Nankoku, Japan

5 Department of Pharmacology, Toxicology & Therapeutics, Division of Physiology & Pathology, Showa University School of Pharmacy, Tokyo, Japan

* These authors have equally contributed to this work

Correspondence to:

Tatsuki R. Kataoka, email:

Keywords: KIR2DL4, inhibitory receptor, Langerhans cell histiocytosis, ERK, SHP-2, Pathology Section

Received: November 10, 2016 Accepted: March 26, 2017 Published: April 07, 2017

Abstract

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 16936