We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy.
- Authors
Murakami, Ichiro; Morimoto, Akira; Oka, Takashi; Kuwamoto, Satoshi; Kato, Masako; Horie, Yasushi; Hayashi, Kazuhiko; Gogusev, Jean; Jaubert, Francis; Imashuku, Shinsaku; Al-Kadar, Lamia; Takata, Katsuyoshi; Yoshino, Tadashi
- 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.
- Subjects
LANGERHANS cells; INTERLEUKIN-17; ADOBE Photoshop (Computer software); IMAGE analysis; IMMUNOFLUORESCENCE
- Publication
Virchows Archiv: European Journal of Pathology, 2013, Vol 462, Issue 2, p219
- ISSN
0945-6317
- Publication type
Article
- DOI
10.1007/s00428-012-1360-6