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IL‐3 is essential for ICOS‐L stabilization on mast cells, and sustains the IL‐33‐induced RORγt(+) T(reg) generation via enhanced IL‐6 induction

IL‐33 is a member of the IL‐1 family. By binding to its receptor ST2 (IL‐33R) on mast cells, IL‐33 induces the MyD88‐dependent activation of the TAK1‐IKK2 signalling module resulting in activation of the MAP kinases p38, JNK1/2 and ERK1/2, and of NFκB. Depending on the kinases activated in these pat...

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Autores principales: Drube, Sebastian, Müller, Sylvia, Weber, Franziska, Wegner, Philine, Böttcher‐Loschinski, Romy, Gaestel, Matthias, Hutloff, Andreas, Kamradt, Thomas, Andreas, Nico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044339/
https://www.ncbi.nlm.nih.gov/pubmed/33427298
http://dx.doi.org/10.1111/imm.13305
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author Drube, Sebastian
Müller, Sylvia
Weber, Franziska
Wegner, Philine
Böttcher‐Loschinski, Romy
Gaestel, Matthias
Hutloff, Andreas
Kamradt, Thomas
Andreas, Nico
author_facet Drube, Sebastian
Müller, Sylvia
Weber, Franziska
Wegner, Philine
Böttcher‐Loschinski, Romy
Gaestel, Matthias
Hutloff, Andreas
Kamradt, Thomas
Andreas, Nico
author_sort Drube, Sebastian
collection PubMed
description IL‐33 is a member of the IL‐1 family. By binding to its receptor ST2 (IL‐33R) on mast cells, IL‐33 induces the MyD88‐dependent activation of the TAK1‐IKK2 signalling module resulting in activation of the MAP kinases p38, JNK1/2 and ERK1/2, and of NFκB. Depending on the kinases activated in these pathways, the IL‐33‐induced signalling is essential for production of IL‐6 or IL‐2. This was shown to control the dichotomy between RORγt(+) and Helios(+) T(regs), respectively. SCF, the ligand of c‐Kit (CD117), can enhance these effects. Here, we show that IL‐3, another growth factor for mast cells, is essential for the expression of ICOS‐L on BMMCs, and costimulation with IL‐3 potentiated the IL‐33‐induced IL‐6 production similar to SCF. In contrast to the enhanced IL‐2 production by SCF‐induced modulation of the IL‐33 signalling, IL‐3 blocked the production of IL‐2. Consequently, IL‐3 shifted the IL‐33‐induced T(reg) dichotomy towards RORγt(+) T(regs) at the expense of RORγt(−) Helios(+) T(regs). However, ICOS‐L expression was downregulated by IL‐33. In line with that, ICOS‐L did not play any important role in the T(reg) modulation by IL‐3/IL‐33‐activated mast cells. These findings demonstrate that different from the mast cell growth factor SCF, IL‐3 can alter the IL‐33‐induced and mast cell‐dependent regulation of T(reg) subpopulations by modulating mast cell‐derived cytokine profiles.
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spelling pubmed-80443392021-04-16 IL‐3 is essential for ICOS‐L stabilization on mast cells, and sustains the IL‐33‐induced RORγt(+) T(reg) generation via enhanced IL‐6 induction Drube, Sebastian Müller, Sylvia Weber, Franziska Wegner, Philine Böttcher‐Loschinski, Romy Gaestel, Matthias Hutloff, Andreas Kamradt, Thomas Andreas, Nico Immunology Original Articles IL‐33 is a member of the IL‐1 family. By binding to its receptor ST2 (IL‐33R) on mast cells, IL‐33 induces the MyD88‐dependent activation of the TAK1‐IKK2 signalling module resulting in activation of the MAP kinases p38, JNK1/2 and ERK1/2, and of NFκB. Depending on the kinases activated in these pathways, the IL‐33‐induced signalling is essential for production of IL‐6 or IL‐2. This was shown to control the dichotomy between RORγt(+) and Helios(+) T(regs), respectively. SCF, the ligand of c‐Kit (CD117), can enhance these effects. Here, we show that IL‐3, another growth factor for mast cells, is essential for the expression of ICOS‐L on BMMCs, and costimulation with IL‐3 potentiated the IL‐33‐induced IL‐6 production similar to SCF. In contrast to the enhanced IL‐2 production by SCF‐induced modulation of the IL‐33 signalling, IL‐3 blocked the production of IL‐2. Consequently, IL‐3 shifted the IL‐33‐induced T(reg) dichotomy towards RORγt(+) T(regs) at the expense of RORγt(−) Helios(+) T(regs). However, ICOS‐L expression was downregulated by IL‐33. In line with that, ICOS‐L did not play any important role in the T(reg) modulation by IL‐3/IL‐33‐activated mast cells. These findings demonstrate that different from the mast cell growth factor SCF, IL‐3 can alter the IL‐33‐induced and mast cell‐dependent regulation of T(reg) subpopulations by modulating mast cell‐derived cytokine profiles. John Wiley and Sons Inc. 2021-01-27 2021-05 /pmc/articles/PMC8044339/ /pubmed/33427298 http://dx.doi.org/10.1111/imm.13305 Text en © 2021 The Authors. Immunology published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Drube, Sebastian
Müller, Sylvia
Weber, Franziska
Wegner, Philine
Böttcher‐Loschinski, Romy
Gaestel, Matthias
Hutloff, Andreas
Kamradt, Thomas
Andreas, Nico
IL‐3 is essential for ICOS‐L stabilization on mast cells, and sustains the IL‐33‐induced RORγt(+) T(reg) generation via enhanced IL‐6 induction
title IL‐3 is essential for ICOS‐L stabilization on mast cells, and sustains the IL‐33‐induced RORγt(+) T(reg) generation via enhanced IL‐6 induction
title_full IL‐3 is essential for ICOS‐L stabilization on mast cells, and sustains the IL‐33‐induced RORγt(+) T(reg) generation via enhanced IL‐6 induction
title_fullStr IL‐3 is essential for ICOS‐L stabilization on mast cells, and sustains the IL‐33‐induced RORγt(+) T(reg) generation via enhanced IL‐6 induction
title_full_unstemmed IL‐3 is essential for ICOS‐L stabilization on mast cells, and sustains the IL‐33‐induced RORγt(+) T(reg) generation via enhanced IL‐6 induction
title_short IL‐3 is essential for ICOS‐L stabilization on mast cells, and sustains the IL‐33‐induced RORγt(+) T(reg) generation via enhanced IL‐6 induction
title_sort il‐3 is essential for icos‐l stabilization on mast cells, and sustains the il‐33‐induced rorγt(+) t(reg) generation via enhanced il‐6 induction
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044339/
https://www.ncbi.nlm.nih.gov/pubmed/33427298
http://dx.doi.org/10.1111/imm.13305
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