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 language | English |
|---|---|
| Pages (from-to) | 219-228 |
| Number of pages | 10 |
| Journal | Virchows Archiv |
| Volume | 462 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2013 |
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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 journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=84877157663&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877157663&partnerID=8YFLogxK
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
JF - Virchows Archiv
SN - 0945-6317
IS - 2
ER -