1. Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the cell growth of Langerhans cell histiocytosis
- Author
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Sanju Iwamoto, Hironori Haga, Akihiko Sugimoto, Koki Moriyoshi, Tatsuki R. Kataoka, Masahiro Hirata, Yusuke Takei, Kazuo Ono, Mariyo Rokutan-Kurata, Ichiro Murakami, and Chiyuki Ueshima
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Adult ,Male ,0301 basic medicine ,Cytoplasm ,Pathology ,medicine.medical_specialty ,Adolescent ,Killer-cell immunoglobulin-like receptor ,Cell ,Gene Expression ,HL-60 Cells ,Cell Line ,KIR2DL4 ,Young Adult ,03 medical and health sciences ,Langerhans cell histiocytosis ,Cell Line, Tumor ,Pathology Section ,Humans ,Medicine ,Phosphorylation ,Child ,Extracellular Signal-Regulated MAP Kinases ,Receptor ,Cell Proliferation ,Cell growth ,business.industry ,Cell Membrane ,Infant ,inhibitory receptor ,Middle Aged ,medicine.disease ,Molecular biology ,Research Paper: Pathology ,ERK ,Histiocytosis, Langerhans-Cell ,030104 developmental biology ,medicine.anatomical_structure ,Receptors, KIR2DL4 ,Oncology ,Cell culture ,Child, Preschool ,SHP-2 ,Female ,business - 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.
- Published
- 2017
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