Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer
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 infl...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/1721.1/101724 https://orcid.org/0000-0001-9307-6116 |
| _version_ | 1826195979694505984 |
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| author | Dubeykovskaya, Zina Si, Yiling Chen, Xiaowei Worthley, Daniel L. Renz, Bernhard W. Urbanska, Aleksandra M. Hayakawa, Yoku Xu, Ting Westphalen, C. Benedikt Dubeykovskiy, Alexander Chen, Duan Friedman, Richard A. Asfaha, Samuel Nagar, Karan Tailor, Yagnesh Muthupalani, Sureshkumar Fox, James G. Kitajewski, Jan Wang, Timothy C. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Dubeykovskaya, Zina Si, Yiling Chen, Xiaowei Worthley, Daniel L. Renz, Bernhard W. Urbanska, Aleksandra M. Hayakawa, Yoku Xu, Ting Westphalen, C. Benedikt Dubeykovskiy, Alexander Chen, Duan Friedman, Richard A. Asfaha, Samuel Nagar, Karan Tailor, Yagnesh Muthupalani, Sureshkumar Fox, James G. Kitajewski, Jan Wang, Timothy C. |
| author_sort | Dubeykovskaya, Zina |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:18:55Z |
| format | Article |
| id | mit-1721.1/101724 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:18:55Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1017242022-09-30T20:21:31Z Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer Dubeykovskaya, Zina Si, Yiling Chen, Xiaowei Worthley, Daniel L. Renz, Bernhard W. Urbanska, Aleksandra M. Hayakawa, Yoku Xu, Ting Westphalen, C. Benedikt Dubeykovskiy, Alexander Chen, Duan Friedman, Richard A. Asfaha, Samuel Nagar, Karan Tailor, Yagnesh Muthupalani, Sureshkumar Fox, James G. Kitajewski, Jan Wang, Timothy C. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Muthupalani, Sureshkumar Fox, James G. 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. 2016-03-16T20:13:58Z 2016-03-16T20:13:58Z 2016-02 2015-09 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/101724 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. https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.1038/ncomms10517 Nature Communications Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Publishing Group |
| spellingShingle | Dubeykovskaya, Zina Si, Yiling Chen, Xiaowei Worthley, Daniel L. Renz, Bernhard W. Urbanska, Aleksandra M. Hayakawa, Yoku Xu, Ting Westphalen, C. Benedikt Dubeykovskiy, Alexander Chen, Duan Friedman, Richard A. Asfaha, Samuel Nagar, Karan Tailor, Yagnesh Muthupalani, Sureshkumar Fox, James G. Kitajewski, Jan Wang, Timothy C. Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer |
| title | Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer |
| title_full | Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer |
| title_fullStr | Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer |
| title_full_unstemmed | Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer |
| title_short | Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer |
| title_sort | neural innervation stimulates splenic tff2 to arrest myeloid cell expansion and cancer |
| url | http://hdl.handle.net/1721.1/101724 https://orcid.org/0000-0001-9307-6116 |
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