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

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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

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Interleukin Receptors
Langerhans Cell Histiocytosis
Interleukin-17
Interleukins
Serum
Langerhans Cells
Lymphoproliferative Disorders

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy. / Murakami, Ichiro; Morimoto, Akira; Oka, Takashi; Kuwamoto, Satoshi; Kato, Masako; Horie, Yasushi; Hayashi, Kazuhiko; Gogusev, Jean; Jaubert, Francis; Imashuku, Shinsaku; Al-Kadar, Lamia Abd; Takata, Katsuyoshi; Yoshino, Tadashi.

In: Virchows Archiv, Vol. 462, No. 2, 02.2013, p. 219-228.

Research output: Contribution to journalArticle

Murakami, I, Morimoto, A, Oka, T, Kuwamoto, S, Kato, M, Horie, Y, Hayashi, K, Gogusev, J, Jaubert, F, Imashuku, S, Al-Kadar, LA, Takata, K & Yoshino, T 2013, 'IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy', Virchows Archiv, vol. 462, no. 2, pp. 219-228. https://doi.org/10.1007/s00428-012-1360-6
Murakami, Ichiro ; Morimoto, Akira ; Oka, Takashi ; Kuwamoto, Satoshi ; Kato, Masako ; Horie, Yasushi ; Hayashi, Kazuhiko ; Gogusev, Jean ; Jaubert, Francis ; Imashuku, Shinsaku ; Al-Kadar, Lamia Abd ; Takata, Katsuyoshi ; Yoshino, Tadashi. / IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy. In: Virchows Archiv. 2013 ; Vol. 462, No. 2. pp. 219-228.
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