title: Increased presence of FOXP3+ regulatory T cells in inflamed muscle of patients with active juvenile dermatomyositis compared to peripheral blood.
abstract: Juvenile dermatomyositis (JDM) is an immune-mediated inflammatory disease affecting the microvasculature of skin and muscle. CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) are key regulators of immune homeostasis. A role for Tregs in JDM pathogenesis has not yet been established. Here, we explored Treg presence and function in peripheral blood and muscle of JDM patients. We analyzed number, phenotype and function of Tregs in blood from JDM patients by flow cytometry and in vitro suppression assays, in comparison to healthy controls and disease controls (Duchenne's Muscular Dystrophy). Presence of Tregs in muscle was analyzed by immunohistochemistry. Overall, Treg percentages in peripheral blood of JDM patients were similar compared to both control groups. Muscle biopsies of new onset JDM patients showed increased infiltration of numbers of T cells compared to Duchenne's muscular dystrophy. Both in JDM and Duchenne's muscular dystrophy the proportion of FOXP3+ T cells in muscles were increased compared to JDM peripheral blood. Interestingly, JDM is not a self-remitting disease, suggesting that the high proportion of Tregs in inflamed muscle do not suppress inflammation. In line with this, peripheral blood Tregs of active JDM patients were less capable of suppressing effector T cell activation in vitro, compared to Tregs of JDM in clinical remission. These data show a functional impairment of Tregs in a proportion of patients with active disease, and suggest a regulatory role for Tregs in JDM inflammation.
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Vercoulen
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands; Division of Allergology, Immunology and Rheumatology, Department of Pediatrics, University Hospital, Lausanne, Switzerland.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Bellutti Enders
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jenny
authors.initials: J
authors.lastname: Meerding
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maud
authors.initials: M
authors.lastname: Plantinga
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Elisabeth F
authors.initials: EF
authors.lastname: Elst
authors.affiliation: Rheumatology Unit, University College London Institute of Child Health, on behalf of the Juvenile Dermatomyositis Research Group (UK and Ireland), London, United Kingdom.
authors.forename: Hemlata
authors.initials: H
authors.lastname: Varsani
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Christa
authors.initials: C
authors.lastname: van Schieveen
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mette H
authors.initials: MH
authors.lastname: Bakker
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Klein
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rianne C
authors.initials: RC
authors.lastname: Scholman
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Spliet
authors.affiliation: Dubowitz Neuromuscular Centre, University College London Institute of Child Health, London, United Kingdom.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ricotti
authors.affiliation: Department Laboratory Medicine, Section Medical Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Hans J P M
authors.initials: HJ
authors.lastname: Koenen
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
authors.affiliation: Rheumatology Unit, University College London Institute of Child Health, on behalf of the Juvenile Dermatomyositis Research Group (UK and Ireland), London, United Kingdom.
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.affiliation: Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Annet
authors.initials: A
authors.lastname: van Royen-Kerkhof
authors.affiliation: Laboratory of Translational Immunology, Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D009132:Muscles / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors