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TGF-ß1 Drives Inflammatory Th Cell But Not Treg Cell Compartment Upon Allergen Exposure.
Musiol, Stephanie; Alessandrini, Francesca; Jakwerth, Constanze A; Chaker, Adam M; Schneider, Evelyn; Guerth, Ferdinand; Schnautz, Benjamin; Grosch, Johanna; Ghiordanescu, Ileana; Ullmann, Julia T; Kau, Josephine; Plaschke, Mirjam; Haak, Stefan; Buch, Thorsten; Schmidt-Weber, Carsten B; Zissler, Ulrich M.
Afiliação
  • Musiol S; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Alessandrini F; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Jakwerth CA; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Chaker AM; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Schneider E; Department of Otorhinolaryngology, Klinikum rechts der Isar, TUM School of Medicine, Technical University Munich, Munich, Germany.
  • Guerth F; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Schnautz B; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Grosch J; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Ghiordanescu I; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Ullmann JT; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Kau J; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Plaschke M; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Haak S; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
  • Buch T; Institute of Laboratory Animal Science, University of Zurich, Zurich, Switzerland.
  • Schmidt-Weber CB; Institute of Laboratory Animal Science, University of Zurich, Zurich, Switzerland.
  • Zissler UM; Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Center Munich, German Research Center for Environmental Health, Members of the German Center of Lung Research (DZL), Munich, Germany.
Front Immunol ; 12: 763243, 2021.
Article em En | MEDLINE | ID: mdl-35069535
ABSTRACT
TGF-ß1 is known to have a pro-inflammatory impact by inducing Th9 and Th17 cells, while it also induces anti-inflammatory Treg cells (Tregs). In the context of allergic airway inflammation (AAI) its dual role can be of critical importance in influencing the outcome of the disease. Here we demonstrate that TGF-ß is a major player in AAI by driving effector T cells, while Tregs differentiate independently. Induction of experimental AAI and airway hyperreactivity in a mouse model with inducible genetic ablation of the gene encoding for TGFß-receptor 2 (Tgfbr2) on CD4+T cells significantly reduced the disease phenotype. Further, it blocked the induction of pro-inflammatory T cell frequencies (Th2, Th9, Th17), but increased Treg cells. To translate these findings into a human clinically relevant context, Th2, Th9 and Treg cells were quantified both locally in induced sputum and systemically in blood of allergic rhinitis and asthma patients with or without allergen-specific immunotherapy (AIT). Natural allergen exposure induced local and systemic Th2, Th9, and reduced Tregs cells, while therapeutic allergen exposure by AIT suppressed Th2 and Th9 cell frequencies along with TGF-ß and IL-9 secretion. Altogether, these findings support that neutralization of TGF-ß represents a viable therapeutic option in allergy and asthma, not posing the risk of immune dysregulation by impacting Tregs cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Alérgenos / Linfócitos T Reguladores / Linfócitos T Auxiliares-Indutores / Fator de Crescimento Transformador beta1 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Alérgenos / Linfócitos T Reguladores / Linfócitos T Auxiliares-Indutores / Fator de Crescimento Transformador beta1 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article