TY - JOUR
T1 - IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy
AU - Murakami, Ichiro
AU - Morimoto, Akira
AU - Oka, Takashi
AU - Kuwamoto, Satoshi
AU - Kato, Masako
AU - Horie, Yasushi
AU - Hayashi, Kazuhiko
AU - Gogusev, Jean
AU - Jaubert, Francis
AU - Imashuku, Shinsaku
AU - Al-Kadar, Lamia Abd
AU - Takata, Katsuyoshi
AU - Yoshino, Tadashi
N1 - Funding Information:
Acknowledgments This work was partly supported by the Histiocytosis Association of America (HAA grant 2009); a Grant-in-aid for Scientific Research (C) 23590426 from the Japanese Ministry of Education, Science, Sports and Culture; Grant for Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan; and a 2011 research grant from the Japan LCH Study Group. We thank Dr. Katsumi Higaki and Dr. Katsumi Nagata (Research Center for Bioscience and Technology, Tottori University) for their help with confocal microscopy and LC/MRM-MS.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Immunofluorescence
KW - Interleukin-17A
KW - Interleukin-17A receptor
KW - Langerhans cell histiocytosis
KW - Photoshop-assisted image analysis
KW - Staining intensity
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U2 - 10.1007/s00428-012-1360-6
DO - 10.1007/s00428-012-1360-6
M3 - Article
C2 - 23269323
AN - SCOPUS:84877157663
VL - 462
SP - 219
EP - 228
JO - Virchows Archiv - Abteilung A Pathologische Anatomie
JF - Virchows Archiv - Abteilung A Pathologische Anatomie
SN - 0945-6317
IS - 2
ER -