PMID- 36164563
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220928
IS  - 2405-5808 (Electronic)
IS  - 2405-5808 (Linking)
VI  - 32
DP  - 2022 Dec
TI  - MDSCs participate in the pathogenesis of diffuse pulmonary hemorrhage in murine 
      lupus through mTOR-FoxO1 signaling.
PG  - 101351
LID - 10.1016/j.bbrep.2022.101351 [doi]
LID - 101351
AB  - Diffuse pulmonary hemorrhage (DPH) is a common respiratory complication in 
      patients with systemic lupus erythematosus (SLE). Our previous study found that 
      myeloid-derived suppressor cells (MDSCs) have an important role in SLE 
      pathogenesis. In this study, we further examined the role of MDSCs in the DPH 
      mice model. We first observed an increased proportion of MDSCs and impaired 
      immunosuppressive function in bronchoalveolar lavage fluid (BALF) and peritoneal 
      cavity in the DPH mice model induced by pristane. By injecting anti-Gr-1 
      antibody, we found that MDSCs clearance can significantly alleviate DPH symptoms. 
      The detection of downstream molecules proved that the mTOR signaling pathway was 
      obviously activated in purified DPH MDSCs. After treatment of DPH model mice with 
      AMPK agonist metformin, mammalian target of rapamycin (mTOR) inhibitor INK128, 
      and rapamycin, respectively, we observed that inhibition of the mTOR signal 
      alleviated DPH symptoms, inhibited the expansion of mononuclear MDSCs (M-MDSCs) 
      and the differentiation of pro-inflammatory M1 macrophages (M1), which, in turn, 
      promoted the expansion of granulocytes MDSCs (G-MDSCs) and differentiation of 
      anti-inflammatory M2 macrophages (M2). We then demonstrated that inhibition of 
      the mTOR signal increased the expansion of G-MDSCs, promoted M-MDSCs 
      differentiation into M2 and inhibited their differentiation into M1 by 
      administering TLR7 agonist R848 in vitro to simulate lupus environment. In 
      addition, we also observed increased forkhead box-O1 (FoxO1) expression in 
      M-MDSCs and macrophages after mTOR signal inhibition, both in vivo and in vitro. 
      After down-regulation of FoxO1 by siRNA transfection, the regulatory effects of 
      mTOR signal inhibition on M-MDSCs, M1 and M2 were reversed. Taken together, 
      inhibition of the AMPK/mTOR signal could alleviate lupus-like diffuse lung injury 
      by inducing M-MDSCs to differentiate into M2 by up-regulating FoxO1.
CI  - (c) 2022 The Authors.
FAU - Tan, Liping
AU  - Tan L
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, 210093, PR China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, PR China.
FAU - Shi, Guoping
AU  - Shi G
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, 210093, PR China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, PR China.
FAU - Zhao, Junyu
AU  - Zhao J
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, 210093, PR China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, PR China.
FAU - Xia, Xiaoyu
AU  - Xia X
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, 210093, PR China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, PR China.
FAU - Li, Dan
AU  - Li D
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, 210093, PR China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, PR China.
FAU - Wang, Saiwen
AU  - Wang S
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, 210093, PR China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, PR China.
FAU - Liang, Jun
AU  - Liang J
AD  - Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The 
      Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR 
      China.
FAU - Hou, Yayi
AU  - Hou Y
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, 210093, PR China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, PR China.
FAU - Dou, Huan
AU  - Dou H
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, 
      Medical School, Nanjing University, Nanjing, 210093, PR China.
AD  - Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, PR China.
LA  - eng
PT  - Journal Article
DEP - 20220922
PL  - Netherlands
TA  - Biochem Biophys Rep
JT  - Biochemistry and biophysics reports
JID - 101660999
PMC - PMC9507990
OTO - NOTNLM
OT  - Diffuse pulmonary hemorrhage
OT  - Forkhead box-O1
OT  - Macrophage
OT  - Mammalian target of rapamycin
OT  - Myeloid-derived suppressor cells
OT  - Systemic lupus erythematosus
COIS- The authors declare that they have no known competing financialinterestsor 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2022/09/28 06:00
MHDA- 2022/09/28 06:01
PMCR- 2022/09/22
CRDT- 2022/09/27 02:02
PHST- 2022/06/21 00:00 [received]
PHST- 2022/09/14 00:00 [revised]
PHST- 2022/09/15 00:00 [accepted]
PHST- 2022/09/27 02:02 [entrez]
PHST- 2022/09/28 06:00 [pubmed]
PHST- 2022/09/28 06:01 [medline]
PHST- 2022/09/22 00:00 [pmc-release]
AID - S2405-5808(22)00151-0 [pii]
AID - 101351 [pii]
AID - 10.1016/j.bbrep.2022.101351 [doi]
PST - epublish
SO  - Biochem Biophys Rep. 2022 Sep 22;32:101351. doi: 10.1016/j.bbrep.2022.101351. 
      eCollection 2022 Dec.