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.

Autor: Drube S; Institut für Immunologie, Universitätsklinikum Jena, Jena, Germany., Müller S; Institut für Immunologie, Universitätsklinikum Jena, Jena, Germany., Weber F; Institut für Immunologie, Universitätsklinikum Jena, Jena, Germany., Wegner P; Institut für Immunologie, Universitätsklinikum Jena, Jena, Germany., Böttcher-Loschinski R; Medizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen, Germany., Gaestel M; Institut für Zellbiochemie, Medizinische Hochschule Hannover, Hannover, Germany., Hutloff A; Institut für Immunologie und Institut für Klinische Molekularbiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany., Kamradt T; Institut für Immunologie, Universitätsklinikum Jena, Jena, Germany., Andreas N; Institut für Immunologie, Universitätsklinikum Jena, Jena, Germany.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2021 May; Vol. 163 (1), pp. 86-97. Date of Electronic Publication: 2021 Jan 27.
DOI: 10.1111/imm.13305
Abstrakt: 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.
(© 2021 The Authors. Immunology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje