EGFR-HIF1α signaling positively regulates the differentiation of IL-9 producing T helper cells

Suyasha Roy, Zaigham Abbas Rizvi, Alexander J. Clarke, Felicity Macdonald, Abhaydeep Pandey, Dietmar Martin Werner Zaiss, Anna Kathrina Simon and Amit Awasthi ()
Additional contact information
Suyasha Roy: Immuno-biology Laboratory, Translational Health Science & Technology Institute
Zaigham Abbas Rizvi: Immuno-biology Laboratory, Translational Health Science & Technology Institute
Alexander J. Clarke: University of Oxford
Felicity Macdonald: University of Edinburgh
Abhaydeep Pandey: Translational Health Science & Technology Institute
Dietmar Martin Werner Zaiss: University of Edinburgh
Anna Kathrina Simon: University of Oxford
Amit Awasthi: Immuno-biology Laboratory, Translational Health Science & Technology Institute

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract 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-β1 and IL-4. Furthermore, our data show that Areg-EGFR signaling induces HIF1α, which binds and transactivates IL-9 and NOS2 promoters in Th9 cells. Loss of EGFR or HIF1α abrogates Th9 cell differentiation and suppresses their anti-tumor functions. Moreover, in line with its reliance on HIF1α expression, metabolomics profiling of Th9 cells revealed that Succinate, a TCA cycle metabolite, promotes Th9 cell differentiation and Th9 cell-mediated tumor regression.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23042-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23042-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23042-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().