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Increased Presence of FOXP3(+) Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood

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...

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Autores principales: Vercoulen, Yvonne, Bellutti Enders, Felicitas, Meerding, Jenny, Plantinga, Maud, Elst, Elisabeth F., Varsani, Hemlata, van Schieveen, Christa, Bakker, Mette H., Klein, Mark, Scholman, Rianne C., Spliet, Wim, Ricotti, Valeria, Koenen, Hans J. P. M., de Weger, Roel A., Wedderburn, Lucy R., van Royen-Kerkhof, Annet, Prakken, Berent J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144849/
https://www.ncbi.nlm.nih.gov/pubmed/25157414
http://dx.doi.org/10.1371/journal.pone.0105353
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author Vercoulen, Yvonne
Bellutti Enders, Felicitas
Meerding, Jenny
Plantinga, Maud
Elst, Elisabeth F.
Varsani, Hemlata
van Schieveen, Christa
Bakker, Mette H.
Klein, Mark
Scholman, Rianne C.
Spliet, Wim
Ricotti, Valeria
Koenen, Hans J. P. M.
de Weger, Roel A.
Wedderburn, Lucy R.
van Royen-Kerkhof, Annet
Prakken, Berent J.
author_facet Vercoulen, Yvonne
Bellutti Enders, Felicitas
Meerding, Jenny
Plantinga, Maud
Elst, Elisabeth F.
Varsani, Hemlata
van Schieveen, Christa
Bakker, Mette H.
Klein, Mark
Scholman, Rianne C.
Spliet, Wim
Ricotti, Valeria
Koenen, Hans J. P. M.
de Weger, Roel A.
Wedderburn, Lucy R.
van Royen-Kerkhof, Annet
Prakken, Berent J.
author_sort Vercoulen, Yvonne
collection PubMed
description 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.
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spelling pubmed-41448492014-08-29 Increased Presence of FOXP3(+) Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood Vercoulen, Yvonne Bellutti Enders, Felicitas Meerding, Jenny Plantinga, Maud Elst, Elisabeth F. Varsani, Hemlata van Schieveen, Christa Bakker, Mette H. Klein, Mark Scholman, Rianne C. Spliet, Wim Ricotti, Valeria Koenen, Hans J. P. M. de Weger, Roel A. Wedderburn, Lucy R. van Royen-Kerkhof, Annet Prakken, Berent J. PLoS One Research Article 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. Public Library of Science 2014-08-26 /pmc/articles/PMC4144849/ /pubmed/25157414 http://dx.doi.org/10.1371/journal.pone.0105353 Text en © 2014 Vercoulen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vercoulen, Yvonne
Bellutti Enders, Felicitas
Meerding, Jenny
Plantinga, Maud
Elst, Elisabeth F.
Varsani, Hemlata
van Schieveen, Christa
Bakker, Mette H.
Klein, Mark
Scholman, Rianne C.
Spliet, Wim
Ricotti, Valeria
Koenen, Hans J. P. M.
de Weger, Roel A.
Wedderburn, Lucy R.
van Royen-Kerkhof, Annet
Prakken, Berent J.
Increased Presence of FOXP3(+) Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood
title Increased Presence of FOXP3(+) Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood
title_full Increased Presence of FOXP3(+) Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood
title_fullStr Increased Presence of FOXP3(+) Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood
title_full_unstemmed Increased Presence of FOXP3(+) Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood
title_short Increased Presence of FOXP3(+) Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood
title_sort increased presence of foxp3(+) regulatory t cells in inflamed muscle of patients with active juvenile dermatomyositis compared to peripheral blood
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144849/
https://www.ncbi.nlm.nih.gov/pubmed/25157414
http://dx.doi.org/10.1371/journal.pone.0105353
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