Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer
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Dubeykovskaya-2016-Neural Innervation.pdf
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1.47 MB
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Author(s)
Dubeykovskaya, Zina
Si, Yiling
Chen, Xiaowei
Worthley, Daniel L.
Renz, Bernhard W.
Urbanska, Aleksandra M.
Hayakawa, Yoku
Xu, Ting
Westphalen, C. Benedikt
Dubeykovskiy, Alexander
Date Issued
February 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Dubeykovskaya, Zina, Yiling Si, Xiaowei Chen, Daniel L. Worthley, Bernhard W. Renz, Aleksandra M. Urbanska, Yoku Hayakawa, et al. “Neural Innervation Stimulates Splenic TFF2 to Arrest Myeloid Cell Expansion and Cancer.” Nat Comms 7 (February 4, 2016): 10517.
Version
Final published version
Abstract
CD11b[superscript +]Gr-1[superscript +] 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
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DOI of Published Version
https://doi.org/10.1038/ncomms10517
