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Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer

Author

Listed:
  • Zina Dubeykovskaya

    (Columbia University)

  • Yiling Si

    (Columbia University)

  • Xiaowei Chen

    (Columbia University)

  • Daniel L. Worthley

    (Columbia University)

  • Bernhard W. Renz

    (Columbia University
    Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich)

  • Aleksandra M. Urbanska

    (Columbia University)

  • Yoku Hayakawa

    (Columbia University)

  • Ting Xu

    (Columbia University)

  • C. Benedikt Westphalen

    (Columbia University)

  • Alexander Dubeykovskiy

    (Columbia University)

  • Duan Chen

    (Norwegian University of Science and Technology)

  • Richard A. Friedman

    (Irving Cancer Research Center, Columbia University)

  • Samuel Asfaha

    (Columbia University)

  • Karan Nagar

    (Columbia University)

  • Yagnesh Tailor

    (Columbia University)

  • Sureshkumar Muthupalani

    (Massachusetts Institute of Technology)

  • James G. Fox

    (Massachusetts Institute of Technology)

  • Jan Kitajewski

    (Herbert Irving Comprehensive Cancer Center, Columbia University)

  • Timothy C. Wang

    (Columbia University)

Abstract

CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) expand in the spleen during cancer and promote progression through suppression of cytotoxic T cells. An anti-inflammatory reflex arc involving the vagus nerve and memory T cells is necessary for resolution of acute inflammation. Failure of this neural circuit could promote procarcinogenic inflammation and altered tumour immunity. Here we show that splenic TFF2, a secreted anti-inflammatory peptide, is released by vagally modulated memory T cells to suppress the expansion of MDSCs through CXCR4. Splenic denervation interrupts the anti-inflammatory neural arc, resulting in the expansion of MDSCs and colorectal cancer. Deletion of Tff2 recapitulates splenic denervation to promote carcinogenesis. Colorectal carcinogenesis could be suppressed through transgenic overexpression of TFF2, adenoviral transfer of TFF2 or transplantation of TFF2-expressing bone marrow. TFF2 is important to the anti-inflammatory reflex arc and plays an essential role in arresting MDSC proliferation. TFF2 offers a potential approach to prevent and to treat cancer.

Suggested Citation

  • Zina Dubeykovskaya & Yiling Si & Xiaowei Chen & Daniel L. Worthley & Bernhard W. Renz & Aleksandra M. Urbanska & Yoku Hayakawa & Ting Xu & C. Benedikt Westphalen & Alexander Dubeykovskiy & Duan Chen &, 2016. "Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10517
    DOI: 10.1038/ncomms10517
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