IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy

Ichiro Murakami, Akira Morimoto, Takashi Oka, Satoshi Kuwamoto, Masako Kato, Yasushi Horie, Kazuhiko Hayashi, Jean Gogusev, Francis Jaubert, Shinsaku Imashuku, Lamia Abd Al-Kadar, Katsuyoshi Takata, Tadashi Yoshino

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Langerhans cell histiocytosis (LCH) is a lymphoproliferative disorder consisting of abnormal Langerhans cell-like cells and other lymphoid cells. LCH presents as either a multisystem LCH (LCH-MS) or a single-system LCH (LCH-SS). Currently, neither the pathogeneses nor the factors that define these disease subclasses have been elucidated. The interleukin (IL)-17A autocrine LCH model and IL-17A-targeted therapies have been proposed and have engendered much controversy. Those authors showed high serum IL-17A levels in LCH and argued that serum IL-17A-dependent fusion activities in vitro, rather than serum IL-17A levels, correlated with LCH severity (i.e. the IL-17A paradox). In contrast, others could not confirm the IL-17A autocrine model. So began the controversy on IL-17A, which still continues. We approached the IL-17A controversy and the IL-17A paradox from a new perspective in considering the expression levels of IL-17A receptor (IL-17RA). We detected higher levels of IL-17RA protein expression in LCH-MS (n = 10) as compared to LCH-SS (n = 9) (P = 0.041) by immunofluorescence. We reconfirmed these data by re-analyzing GSE16395 mRNA data. We found that serum levels of IL-17A were higher in LCH (n = 38) as compared to controls (n = 20) (P = 0.005) with no significant difference between LCH subclasses. We propose an IL-17A endocrine model and stress that changes in IL-17RA expression levels are important for defining LCH subclasses. We hypothesize that these IL-17RA data could clarify the IL-17A controversy and the IL-17A paradox. As a potential treatment of LCH-MS, we indicate the possibility of an IL-17RA-targeted therapy.

Original languageEnglish
Pages (from-to)219-228
Number of pages10
JournalVirchows Archiv
Volume462
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • Immunofluorescence
  • Interleukin-17A
  • Interleukin-17A receptor
  • Langerhans cell histiocytosis
  • Photoshop-assisted image analysis
  • Staining intensity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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