Fas signaling-mediated TH9 cell differentiation favors bowel inflammation and antitumor functions

Yingying Shen, Zhengbo Song, Xinliang Lu, Zeyu Ma, Chaojie Lu, Bei Zhang, Yinghu Chen, Meng Duan, Lionel Apetoh, Xu Li, Jufeng Guo, Ying Miao, Gensheng Zhang, Diya Yang, Zhijian Cai () and Jianli Wang ()
Additional contact information
Yingying Shen: Zhejiang University School of Medicine
Zhengbo Song: Zhejiang Cancer Hospital
Xinliang Lu: Zhejiang University School of Medicine
Zeyu Ma: Zhejiang University School of Medicine
Chaojie Lu: Zhejiang University School of Medicine
Bei Zhang: Zhejiang University School of Medicine
Yinghu Chen: Zhejiang University School of Medicine
Meng Duan: Zhejiang University
Lionel Apetoh: INSERM
Xu Li: Westlake University
Jufeng Guo: Zhejiang University School of Medicine
Ying Miao: Qingdao Municipal Hospital
Gensheng Zhang: Zhejiang University School of Medicine
Diya Yang: Zhejiang Sci-Tech University
Zhijian Cai: Zhejiang University School of Medicine
Jianli Wang: Zhejiang University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes TH9 cell differentiation by activating NF-κB via Ca2+-dependent PKC-β activation. In addition, PKC-β also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fas-induced TH9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing TH9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated TH9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high TH9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4+ T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for TH9 cell induction and cancer therapy.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10889-4 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:10:y:2019:i:1:d:10.1038_s41467-019-10889-4

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

DOI: 10.1038/s41467-019-10889-4

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 ().