Dexamethasone-Induced Myeloid-Derived Suppressor Cells Prolong Allo Cardiac Graft Survival through iNOS- and Glucocorticoid Receptor-Dependent Mechanism

Frontiers in Immunology
Yang ZhaoJun-Feng Du

Abstract

How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs) are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro. However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance. Herein, we combined dexamethasone (Dex), which is a classic immune regulatory drug in the clinic, with common MDSCs inducing cytokine granulocyte macrophage colony stimulating factor (GM-CSF) to generate MDSCs in vitro. Addition of Dex into GM-CSF system specifically increased the number of CD11b+ Gr-1int/low MDSCs with an enhanced immunosuppressive function in vitro. Adoptive transfer of these MDSCs significantly prolonged heart allograft survival and also favored the expansion of regulatory T cells in vivo. Mechanistic studies showed that inducible nitric oxide sythase (iNOS) signaling was required for MDSCs in the control of T-cell response and glucocorticoid receptor (GR) signaling played a critical role i...Continue Reading

References

Mar 27, 2003·Nature Reviews. Immunology·Kathryn J Wood, Shimon Sakaguchi
Dec 3, 2003·Nature Medicine·Zihao WuLaurence A Turka
Jan 2, 2004·Nature Medicine·Hugh Auchincloss
Jan 6, 2004·Nature Reviews. Immunology·Holger Hackstein, Angus W Thomson
Aug 2, 2006·The Journal of Experimental Medicine·Sonya M AbrahamAndrew R Clark
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heth R TurnquistAngus W Thomson
Jul 14, 2007·Nature Reviews. Immunology·Adrian E Morelli, Angus W Thomson
Apr 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Youmin KangGuoxing Zheng
Feb 7, 2009·Nature Reviews. Immunology·Dmitry I Gabrilovich, Srinivas Nagaraj
Jun 17, 2010·The Journal of Clinical Investigation·Mercedes Rodriguez GarciaJordi C Ochando
Aug 14, 2010·Human Immunology·Peter BorosJonathan S Bromberg
Oct 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bingjiao YinPing-Ying Pan
Jul 12, 2011·Seminars in Immunology·Mohamed Ezzelarab, Angus W Thomson
Sep 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heth R TurnquistAngus W Thomson
Nov 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ulrike BaschantJan P Tuckermann
Sep 25, 2012·European Journal of Immunology·Guoxing ZhengAoshuang Chen
Nov 16, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eva SchleckerAdelheid Cerwenka
Oct 10, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A W Thomson, H R Turnquist
Oct 10, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Y LuanB Murphy
May 23, 2014·Science Translational Medicine·Steven L HighfillCrystal L Mackall
Jan 9, 2015·Journal of the American Society of Nephrology : JASN·Limin LiKe Zen
May 7, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·T NakamuraE Ashihara
Sep 13, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peter HsuRalph Nanan
May 6, 2016·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Chenlu HanYong Zhao
Jun 28, 2016·Vaccines·Justin M DavidClaudia Palena
Jan 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jan Broder EnglerManuel A Friese

❮ Previous
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Citations

Jul 12, 2018·International Journal of Cancer. Journal International Du Cancer·Zhongnan YinLixiang Xue
May 6, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Fan YangYong Zhao
Apr 14, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Young S LeeJoseph R Scalea
Dec 18, 2018·Frontiers in Immunology·Snehil BudhwarKiran Singh
May 31, 2019·Scientific Reports·Monika KustermannGudrun Strauss
Aug 15, 2018·International Journal of Molecular Sciences·Tsukasa Nakamura, Hidetaka Ushigome
Dec 20, 2018·Frontiers in Immunology·Min LiShengjun Wang
Sep 12, 2019·Frontiers in Immunology·Jan M EhrchenKatarzyna Barczyk-Kahlert
Jul 31, 2018·Journal of Immunology Research·Fan YangYong Zhao
Apr 12, 2019·International Journal of Molecular Sciences·Kaiwen MuDavid D Kitts
Sep 7, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Yuerong RenYan He
Jan 9, 2021·International Immunopharmacology·Feilong ZhangWei Wang
Aug 21, 2020·The Journal of Clinical Investigation·Sabine MuellerHideho Okada
Mar 29, 2020·International Immunopharmacology·Peng CaoYong Zhao
Mar 16, 2021·Frontiers in Immunology·Jingming Zhuang, Jiangang Hou
Mar 28, 2021·Cancer Communications·Cheng CuiLi Fu

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
FACS
FCS
PCR

Software Mentioned

FCS express

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