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

• Published in: Virchows Archiv : an international journal of pathology Vol. 462; no. 2; pp. 219 - 228
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2013; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Child; Child, Preschool; Female; Gene Expression Regulation, Neoplastic; Histiocytosis, Langerhans-Cell - classification; Histiocytosis, Langerhans-Cell - diagnosis; Histiocytosis, Langerhans-Cell - metabolism; Humans; In Vitro Techniques; Infant; Infant, Newborn; Interleukin-17 - metabolism; Langerhans Cells - metabolism; Langerhans Cells - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Models, Biological; Original Article; Pathology; Receptors, Interleukin-17 - metabolism; Severity of Illness Index; Signal Transduction; Young Adult; Interleukin-17A receptor; Interleukin-17A; Photoshop-assisted image analysis; Immunofluorescence; Langerhans cell histiocytosis; Staining intensity
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-012-1360-6

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.