Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis
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- Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17-Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.…
Autor(en): | Giovanni Almanzar, Matthias Klein, Marc Schmalzing, Deborah Hilligardt, Nady El Hajj, Hermann Kneitz, Vanessa Wild, Andreas Rosenwald, Sandrine Benoit, Henning Hamm, Hans-Peter Tony, Thomas Haaf, Matthias Goebeler, Martina Prelog |
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URN: | urn:nbn:de:bvb:20-opus-196577 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Kinderklinik und Poliklinik |
Medizinische Fakultät / Pathologisches Institut | |
Medizinische Fakultät / Institut für Humangenetik | |
Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie | |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | International Archives of Allergy and Immunology |
ISSN: | 1018-2438 |
ISSN: | 1423-0097 |
Erscheinungsjahr: | 2016 |
Band / Jahrgang: | 171 |
Heft / Ausgabe: | 2 |
Seitenangabe: | 141-154 |
Originalveröffentlichung / Quelle: | International Archives of Allergy and Immunology 2016;171(2):141–154 DOI: 10.1159/000450949 |
DOI: | https://doi.org/10.1159/000450949 |
PubMed-ID: | https://pubmed.ncbi.nlm.nih.gov/27902985 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Th17; Tregs; methylation; suppression; systemic sclerosis |
Datum der Freischaltung: | 20.08.2021 |
Datum der Erstveröffentlichung: | 01.12.2016 |
Anmerkungen: | This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. |
Lizenz (Deutsch): | Deutsches Urheberrecht |