| First Author | Roy S | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 3182 |
| PubMed ID | 34075041 | Mgi Jnum | J:324487 |
| Mgi Id | MGI:6725339 | Doi | 10.1038/s41467-021-23042-x |
| Citation | Roy S, et al. (2021) EGFR-HIF1alpha signaling positively regulates the differentiation of IL-9 producing T helper cells. Nat Commun 12(1):3182 |
| abstractText | Interleukin 9 (IL-9)-producing helper T (Th9) cells are essential for inducing anti-tumor immunity and inflammation in allergic and autoimmune diseases. Although transcription factors that are essential for Th9 cell differentiation have been identified, other signaling pathways that are required for their generation and functions are yet to be explored. Here, we identify that Epidermal Growth Factor Receptor (EGFR) is essential for IL-9 induction in helper T (Th) cells. Moreover, amphiregulin (Areg), an EGFR ligand, is critical for the amplification of Th9 cells induced by TGF-beta1 and IL-4. Furthermore, our data show that Areg-EGFR signaling induces HIF1alpha, which binds and transactivates IL-9 and NOS2 promoters in Th9 cells. Loss of EGFR or HIF1alpha abrogates Th9 cell differentiation and suppresses their anti-tumor functions. Moreover, in line with its reliance on HIF1alpha expression, metabolomics profiling of Th9 cells revealed that Succinate, a TCA cycle metabolite, promotes Th9 cell differentiation and Th9 cell-mediated tumor regression. |
