S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4–ERK1/2 Signaling
Myeloid-derived suppressor cells (MDSCs) often expand during cancer or chronic inflammation and dampen immune responses. However, mechanisms underlying their capacity to escape intrinsic apoptosis in the inflammatory environment are still largely unknown. In this study, we investigated this in mouse...
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doaj-9222ae7511d241e6a7c18c5482c612422020-11-24T20:56:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00388342715S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4–ERK1/2 SignalingQingcui Li0Qingcui Li1Chengliang Dai2Rui Xue3Peigang Wang4Lin Chen5Yijie Han6Ulrike Erben7Ulrike Erben8Zhihai Qin9Zhihai Qin10Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaMedical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaMedical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaMedical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaMyeloid-derived suppressor cells (MDSCs) often expand during cancer or chronic inflammation and dampen immune responses. However, mechanisms underlying their capacity to escape intrinsic apoptosis in the inflammatory environment are still largely unknown. In this study, we investigated this in mouse tumor models with MDSC accumulation. Spontaneous rejection of tumors implanted into mice deficient for the small Ca2+-binding protein S100A4 (S100A4−/−) was accompanied by low numbers of peripheral MDSCs. This was independent of S100A4 expression on tumor cells. In contrast, MDSCs from S100A4−/− tumor-bearing mice showed a diminished resistance to the induction of intrinsic apoptosis. Further studies demonstrated that S100A4 protects MDSCs from apoptosis through toll-like receptor-4/extracellular signal-regulated kinase-dependent caspase-9 inhibition. The finding that S100A4 is critical for MDSC survival in inflammatory environments might have important implications for the clinical treatment of cancer or inflammation-related diseases.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00388/fullS100A4myeloid-derived suppressor cellsintrinsic apoptosistoll-like receptor-4ERK1/2 signaling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qingcui Li Qingcui Li Chengliang Dai Rui Xue Peigang Wang Lin Chen Yijie Han Ulrike Erben Ulrike Erben Zhihai Qin Zhihai Qin |
spellingShingle |
Qingcui Li Qingcui Li Chengliang Dai Rui Xue Peigang Wang Lin Chen Yijie Han Ulrike Erben Ulrike Erben Zhihai Qin Zhihai Qin S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4–ERK1/2 Signaling Frontiers in Immunology S100A4 myeloid-derived suppressor cells intrinsic apoptosis toll-like receptor-4 ERK1/2 signaling |
author_facet |
Qingcui Li Qingcui Li Chengliang Dai Rui Xue Peigang Wang Lin Chen Yijie Han Ulrike Erben Ulrike Erben Zhihai Qin Zhihai Qin |
author_sort |
Qingcui Li |
title |
S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4–ERK1/2 Signaling |
title_short |
S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4–ERK1/2 Signaling |
title_full |
S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4–ERK1/2 Signaling |
title_fullStr |
S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4–ERK1/2 Signaling |
title_full_unstemmed |
S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4–ERK1/2 Signaling |
title_sort |
s100a4 protects myeloid-derived suppressor cells from intrinsic apoptosis via tlr4–erk1/2 signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-03-01 |
description |
Myeloid-derived suppressor cells (MDSCs) often expand during cancer or chronic inflammation and dampen immune responses. However, mechanisms underlying their capacity to escape intrinsic apoptosis in the inflammatory environment are still largely unknown. In this study, we investigated this in mouse tumor models with MDSC accumulation. Spontaneous rejection of tumors implanted into mice deficient for the small Ca2+-binding protein S100A4 (S100A4−/−) was accompanied by low numbers of peripheral MDSCs. This was independent of S100A4 expression on tumor cells. In contrast, MDSCs from S100A4−/− tumor-bearing mice showed a diminished resistance to the induction of intrinsic apoptosis. Further studies demonstrated that S100A4 protects MDSCs from apoptosis through toll-like receptor-4/extracellular signal-regulated kinase-dependent caspase-9 inhibition. The finding that S100A4 is critical for MDSC survival in inflammatory environments might have important implications for the clinical treatment of cancer or inflammation-related diseases. |
topic |
S100A4 myeloid-derived suppressor cells intrinsic apoptosis toll-like receptor-4 ERK1/2 signaling |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00388/full |
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