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

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, Richard A. Friedman, Samuel Asfaha, Karan Nagar, Yagnesh Tailor, Sureshkumar Muthupalani, James G. Fox, Jan Kitajewski and Timothy C. Wang ()
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Zina Dubeykovskaya: Columbia University
Yiling Si: Columbia University
Xiaowei Chen: Columbia University
Daniel L. Worthley: Columbia University
Bernhard W. Renz: Columbia University
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

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10517

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DOI: 10.1038/ncomms10517

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