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

Drube S, Müller S, Weber F, Wegner P, Böttcher-Loschinski R, Gaestel M, Hutloff A, Kamradt T, Andreas N (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Immunology Wiley-Blackwell

DOI: 10.1111/imm.13305

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.

Authors with CRIS profile

Romy Böttcher-Loschinski Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Universitätsklinikum Jena DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE)

How to cite

APA:

Drube, S., Müller, S., Weber, F., Wegner, P., Böttcher-Loschinski, R., Gaestel, M.,... Andreas, N. (2021). 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. https://doi.org/10.1111/imm.13305

MLA:

Drube, Sebastian, et al. "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 (2021).

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