IL-4 and IL-13 Guide Early Thymic Progenitors To Mature toward Dendritic Cells.

ABSTRACT: Recently we reported that IL-4 and IL-13 signaling in murine early thymic progenitors (ETPs) expressing the heteroreceptor (HR) comprising IL-4 receptor ? (IL-4R?) and IL-13 receptor ? 1 (IL-13R?1) activate STAT6 and inhibit ETP maturation potential toward T cells. In this study, we asked whether IL-4 and IL-13 signaling through the HR mobilizes other STAT molecules to shape ETP fate decision. The findings indicate that HR+ ETPs undergoing cytokine signaling display increased STAT1, but not STAT3, phosphorylation in addition to STAT6 activation. In parallel, the ETPs had a STAT1-dependent heightened expression of IRF-8, a transcription factor essential for development of CD8?+ dendritic cells (DCs). Interestingly, STAT1 phosphorylation and IRF-8 upregulation, which are independent of STAT6 activation, guided ETP maturation toward myeloid cells with a CD8?+ DC phenotype. Furthermore, these CD8?+ DCs display a thymic resident phenotype, as they did not express SIRP?, a molecule presumed to be involved in cell migration. These findings suggest that IL-4 and IL-13 cytokine-induced HR signaling provides a double-edged sword that simultaneously blocks T cell lineage potential but advances myeloid maturation that could impact T cell selection and central tolerance.

SUBMITTER: Barik S 

PROVIDER: S-EPMC6219934 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature