IL-3 is essential for ICOS-L stabilization on mast cells, and sustains the IL-33-induced RORγt+ Treg generation via enhanced IL-6 induction.
Immunology
; 163(1): 86-97, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33427298
ABSTRACT
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+ Tregs , 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 Treg dichotomy towards RORγt+ Tregs at the expense of RORγt- Helios+ Tregs . However, ICOS-L expression was downregulated by IL-33. In line with that, ICOS-L did not play any important role in the Treg 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 Treg subpopulations by modulating mast cell-derived cytokine profiles.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-6
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Interleucina-3
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Linfócitos T Reguladores
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Comunicação Parácrina
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Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares
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Ligante Coestimulador de Linfócitos T Induzíveis
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Interleucina-33
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Mastócitos
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article