title: IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy.
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.
authors.affiliation: Division of Molecular Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan. ichiro.murakami.09@gmail.com
authors.forename: Ichiro
authors.initials: I
authors.lastname: Murakami
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Oka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuwamoto
authors.forename: Masako
authors.initials: M
authors.lastname: Kato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Horie
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Jean
authors.initials: J
authors.lastname: Gogusev
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
authors.forename: Lamia Abd
authors.initials: LA
authors.lastname: Al-Kadar
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006646:Histiocytosis, Langerhans-Cell / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D020381:Interleukin-17 / Q000378:metabolism*; D007801:Langerhans Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D053722:Receptors, Interleukin-17 / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C109985:IL17RA protein, human; D020381:Interleukin-17; D053722:Receptors, Interleukin-17