title: Detection of IL-17A-producing peripheral blood monocytes in Langerhans cell histiocytosis patients.
abstract: Langerhans cell histiocytosis (LCH) is a rare disease of unknown cause with manifestations ranging from isolated granulomatous lesions to life-threatening multi-system organ involvement. This disorder is further characterized by infiltration of immune cells in affected tissues and an association with interleukin (IL)-17A has been reported. Here, we investigated the presence of IL-17A-producing cells among peripheral blood mononuclear cells isolated from LCH patients and observed a high percentage of IL-17A(+) monocytes in peripheral blood of LCH patients compared to controls. The IL-17A(+) monocytes were also positive for the transcription factor retinoic acid orphan receptor (ROR) γt and showed increased mRNA levels for both IL-17A and RORγt. Notably, IL-17A was produced by all monocyte subsets and the expression level was positively associated with LCH disease activity. These data support a role for monocytes in the pathogenesis of LCH. Future therapeutic approaches may consider identification of patients who may benefit from IL-17A-targeted interventions.
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. Electronic address: Magdalini.Lourda@ki.se.
authors.forename: Magda
authors.initials: M
authors.lastname: Lourda
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Selma
authors.initials: S
authors.lastname: Olsson-Åkefeldt
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Désirée
authors.initials: D
authors.lastname: Gavhed
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Björnfot
authors.affiliation: Department of Pediatrics, University Hospital of Aarhus at Skejby, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Clausen
authors.affiliation: Department of Pediatrics, Norrland's University Hospital, University of Umeå, Umeå, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hjalmars
authors.affiliation: Department of Pediatric Haematology and Oncology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Clinical Sciences, Department of Paediatrics, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Sabel
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité; INSERM UMR717; Assistance Publique Hôpitaux de Paris, Service de Pneumologie, Hôpital Saint Louis, Paris, France.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Tazi
authors.affiliation: Istituto Toscano Tumori (I.T.T.), Florence, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.affiliation: CNRS, UMR5239, Laboratoire de Biologie Moléculaire de la Cellule, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université de Lyon, Lyon, France; Université de Lyon 1, Villeurbanne, France; Institut Universitaire de France, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Delprat
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Svensson
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006646:Histiocytosis, Langerhans-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D007958:Leukocyte Count; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D020381:Interleukin-17; D018950:Lipopolysaccharide Receptors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3
keywords: Interleukin-17A;; Langerhans cell histiocytosis;; Monocytes;; Retinoic acid orphan receptor C; Retinoic acid orphan receptor γt;