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

ABSTRACT: Interleukin 4 (IL-4) is a critical cytokine implicated with T_H2 immune reactions, which are linked to pathologic conditions of allergic diseases. In that context, the initiation of T_H2 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, Fc?RI. 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 Fc?RI. In summary, our findings indicate an important regulatory role of IL-4 on in vitro-differentiated mouse basophils enhancing their survival and stabilizing Fc?RI 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.

SUBMITTER: Reinhart R 

PROVIDER: S-EPMC6006176 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature