IL-4 enhances survival of in vitro-differentiated mouse basophils through transcription-independent signaling downstream of PI3K.

Reinhart, Ramona; Kaufmann, Thomas (2018). IL-4 enhances survival of in vitro-differentiated mouse basophils through transcription-independent signaling downstream of PI3K. Cell death & disease, 9(7), p. 713. Nature Publishing Group 10.1038/s41419-018-0754-z

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Interleukin 4 (IL-4) is a critical cytokine implicated with T2 immune reactions, which are linked to pathologic conditions of allergic diseases. In that context, the initiation of T2 responses can critically depend on early basophil-derived IL-4 to activate T-cell responses, which then amplify IL-4 secretion. As a pleiotropic cytokine, IL-4 acts on a broad variety of hematopoietic and non-hematopoietic cells. However, the effect of IL-4 on basophils themselves, which are emerging as relevant players in allergic as well as autoimmune diseases, was only scarcely addressed so far. Here we used in vitro-differentiated mouse basophils to investigate the direct effects of IL-4 on cellular viability and surface expression of the high-affinity receptor for IgE, FcεRI. We observed that IL-4 elicits pronounced pro-survival signaling in basophils, delaying spontaneous apoptosis in vitro to a degree comparable to the known pro-survival effects of IL-3. Our data indicate that IL-4-mediated survival depends on PI3K/AKT signaling and-in contrast to IL-3-seems to be largely independent of transcriptional changes but effectuated by post-translational mechanisms affecting BCL-2 family members among others. Additionally, we found that IL-4 signaling has a stabilizing effect on the surface expression levels of the critical basophil activation receptor FcεRI. In summary, our findings indicate an important regulatory role of IL-4 on in vitro-differentiated mouse basophils enhancing their survival and stabilizing FcεRI receptor expression through PI3K-dependent signaling. A better understanding of the regulation of basophil survival will help to define promising targets and consequently treatment strategies in basophil-driven diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Reinhart, Ramona and Kaufmann, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-4889

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Jana Berger

Date Deposited:

10 Jul 2018 09:16

Last Modified:

11 Mar 2021 06:38

Publisher DOI:

10.1038/s41419-018-0754-z

PubMed ID:

29915306

BORIS DOI:

10.7892/boris.118418

URI:

https://boris.unibe.ch/id/eprint/118418

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