박성규 (광주과학기술원, 현 서울대학교 약학대학) | 상위피인용논문 > 한빛사

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광주과학기술원, 현 서울대학교 약학대학

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Cell Reports, Dec 20 2016, 17 (12) S2211-1247(16)31636-9 | https://doi.org/10.1016/j.celrep.2016.11.062 Myeloid-Derived Suppressor Cells Are Controlled by Regulatory T Cells via TGF-β during Murine Colitis

Cho-Rong Lee ¹, Yewon Kwak ¹, Taewoo Yang ¹, Jung Hyun Han ², Sang-Heon Park¹, Michael B. Ye ³, Wongeun Lee ¹, Kyu-Young Sim ¹, Jung-Ah Kang ¹, Yong-Chul Kim ^{1 2}, Sarkis K. Mazmanian ⁴, Sung-Gyoo Park ^{1 2 5 *}

¹School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea
²Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea
³School of Liberal Arts and Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea
⁴Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
⁵Lead contact

^*Corresponding author: correspondence to Sung-Gyoo Park

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.

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