| First Author | Barik S | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 10 | Pages | 2947-2958 |
| PubMed ID | 30291166 | Mgi Jnum | J:267706 |
| Mgi Id | MGI:6258066 | Doi | 10.4049/jimmunol.1701186 |
| Citation | Barik S, et al. (2018) IL-4 and IL-13 Guide Early Thymic Progenitors To Mature toward Dendritic Cells. J Immunol 201(10):2947-2958 |
| abstractText | Recently we reported that IL-4 and IL-13 signaling in murine early thymic progenitors (ETPs) expressing the heteroreceptor (HR) comprising IL-4 receptor alpha (IL-4Ralpha) and IL-13 receptor alpha 1 (IL-13Ralpha1) 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 CD8alpha(+) dendritic cells (DCs). Interestingly, STAT1 phosphorylation and IRF-8 upregulation, which are independent of STAT6 activation, guided ETP maturation toward myeloid cells with a CD8alpha(+) DC phenotype. Furthermore, these CD8alpha(+) DCs display a thymic resident phenotype, as they did not express SIRPalpha, 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. |
