title: Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1β expression and release.
abstract: Chronic recurrent multifocal osteomyelitis (CRMO) is characterized by reduced activation of protein kinases ERK1 and 2 in monocytes resulting in impaired IL-10 expression. IL10 and its homologs IL19 and IL20 are organized in the IL10 cluster on chromosome 1q32. IL-10 and IL-19 are immune-regulatory cytokines, while IL-20 acts in a pro-inflammatory manner. The NLRP3 inflammasome, a multi-protein complex forming in response to innate stimuli, mediates IL-1β cleavage and release. Here, we investigated IL-10-related cytokine expression in CRMO monocytes, underlying molecular events, and effects on inflammatory responses. We observed reduced anti-inflammatory IL-10 and IL-19 expression, and enhanced IL-20 expression in CRMO monocytes. Reduced IL-10 and IL-19 expression was associated with impaired Sp-1 recruitment to regulatory regions, contributing to NLRP3 inflammasome activation, which may induce inflammatory bone-loss. Our findings underscore the importance of balanced receptor-, cell-, and tissue-specific cytokine expression for immune homeostasis, providing additional arguments for cytokine blocking strategies in CRMO.
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Hofmann
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: A S
authors.initials: AS
authors.lastname: Kubasch
authors.affiliation: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ioannidis
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Rösen-Wolff
authors.affiliation: Vivantes Klinikum Friedrichshain, Children's Hospital, Berlin, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Girschick
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital, University of Würzburg, Würzburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Morbach
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany; Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: Christian.hedrich@uniklinikum-dresden.de.
authors.forename: C M
authors.initials: CM
authors.lastname: Hedrich
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002648:Child; D019175:DNA Methylation; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010019:Osteomyelitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C421250:IL19 protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D007378:Interleukins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D016329:Sp1 Transcription Factor; D016753:Interleukin-10; D048049:Extracellular Signal-Regulated MAP Kinases; C422042:interleukin 20
keywords: Bone; CNO; CRMO; Cytokine; IL-10; Inflammasome; Inflammation