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Myeloid-Derived Suppressor Cells Are Controlled by Regulatory T Cells via TGF-β during Murine Colitis

Lee, Cho-Rong and Kwak, Yewon and Yang, Taewoo and Han, Jung Hyun and Park, Sang-Heon and Ye, Michael B. and Lee, Wongeun and Sim, Kyu-Young and Kang, Jung-Ah and Kim, Yong-Chul and Mazmanian, Sarkis K. and Park, Sung-Gyoo (2016) Myeloid-Derived Suppressor Cells Are Controlled by Regulatory T Cells via TGF-β during Murine Colitis. Cell Reports, 17 (12). pp. 3219-3232. ISSN 2211-1247. https://resolver.caltech.edu/CaltechAUTHORS:20170104-140105716

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Abstract

Myeloid-derived suppressor cells (MDSCs) are well known regulators of regulatory T cells (Treg cells); however, the direct regulation of MDSCs by Treg cells has not been well characterized. We find that colitis caused by functional deficiency of Treg cells leads to altered expansion and reduced function of MDSCs. During differentiation of MDSCs in vitro from bone marrow cells, Treg cells enhanced MDSC function and controlled their differentiation through a mechanism involving transforming growth factor-β (TGF-β). TGF-β-deficient Treg cells were not able to regulate MDSC function in an experimentally induced model of colitis. Finally, we evaluated the therapeutic effect of TGF-β-mediated in-vitro-differentiated MDSCs on colitis. Adoptive transfer of MDSCs that differentiated with TGF-β led to better colitis prevention than the transfer of MDSCs that differentiated without TGF-β. Our results demonstrate an interaction between Treg cells and MDSCs that contributes to the regulation of MDSC proliferation and the acquisition of immunosuppressive functions.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.celrep.2016.11.062DOIArticle
http://www.sciencedirect.com/science/article/pii/S2211124716316369PublisherArticle
ORCID:
AuthorORCID
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2016 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received: March 18, 2015; Revised: January 7, 2016; Accepted: November 20, 2016; Published: December 20, 2016. We would like to thank Dr. S. Ghosh (Columbia University) and Dr. M. Kasuga (Kobe University) for the PDK1 conditional knockout mice and Keesook Lee (Chonnam National University) for the Tgfbr2^(flox/flox) mice. This work was supported by a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HI14C1466) and partly by the National Research Foundation of Korea (NRF-2016R1A2B4008819 and NRF-2016R1A5A1007318).
Funders:
Funding AgencyGrant Number
Korea Health Industry Development InstituteUNSPECIFIED
Ministry of Health and Welfare (Korea)HI14C1466
National Research Foundation of KoreaNRF-2016R1A2B4008819
National Research Foundation of KoreaNRF-2016R1A5A1007318
Subject Keywords:Treg cell; MDSC; inflammation; colitis; TGF-β
Issue or Number:12
Record Number:CaltechAUTHORS:20170104-140105716
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170104-140105716
Official Citation:Cho-Rong Lee, Yewon Kwak, Taewoo Yang, Jung Hyun Han, Sang-Heon Park, Michael B. Ye, Wongeun Lee, Kyu-Young Sim, Jung-Ah Kang, Yong-Chul Kim, Sarkis K. Mazmanian, Sung-Gyoo Park, Myeloid-Derived Suppressor Cells Are Controlled by Regulatory T Cells via TGF-β during Murine Colitis, Cell Reports, Volume 17, Issue 12, 20 December 2016, Pages 3219-3232, ISSN 2211-1247, http://dx.doi.org/10.1016/j.celrep.2016.11.062. (http://www.sciencedirect.com/science/article/pii/S2211124716316369)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73217
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:04 Jan 2017 22:10
Last Modified:03 Oct 2019 16:25

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