| First Author | Barik S | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 8 | Pages | 2767-2776 |
| PubMed ID | 28893952 | Mgi Jnum | J:251194 |
| Mgi Id | MGI:6103055 | Doi | 10.4049/jimmunol.1700498 |
| Citation | Barik S, et al. (2017) IL-4/IL-13 Signaling Inhibits the Potential of Early Thymic Progenitors To Commit to the T Cell Lineage. J Immunol 199(8):2767-2776 |
| abstractText | Early thymic progenitors (ETPs) are endowed with diverse potencies and can give rise to myeloid and lymphoid lineage progenitors. How the thymic environment guides ETP commitment and maturation toward a specific lineage remains obscure. We have previously shown that ETPs expressing the heteroreceptor (HR) comprising IL-4Ralpha and IL-13Ralpha1 give rise to myeloid cells but not T cells. In this article, we show that signaling through the HR inhibits ETP maturation to the T cell lineage but enacts commitment toward the myeloid cells. Indeed, HR(+) ETPs, but not HR(-) ETPs, exhibit activated STAT6 transcription factor, which parallels with downregulation of Notch1, a critical factor for T cell development. Meanwhile, the myeloid-specific transcription factor C/EBPalpha, usually under the control of Notch1, is upregulated. Furthermore, in vivo inhibition of STAT6 phosphorylation restores Notch1 expression in HR(+) ETPs, which regain T lineage potential. In addition, upon stimulation with IL-4 or IL-13, HR(-) ETPs expressing virally transduced HR also exhibit STAT6 phosphorylation and downregulation of Notch1, leading to inhibition of lymphoid, but not myeloid, lineage potential. These observations indicate that environmental cytokines play a role in conditioning ETP lineage choice, which would impact T cell development. |
