Myeloid-derived suppressor cell function is diminished in aspirin-triggered allergic airway hyperresponsiveness in mice

Shi, Maohua; Shi, Guochao; Tang, Juan; Kong, Deping; Bao, Yefeng; Xiao, Bing; Zuo, Caojian; Wang, Tai; Wang, Qingsong; Shen, Yujun; Wang, Hui; Funk, Colin D.; Zhou, Jie; Yu, Ying

doi:10.1016/j.jaci.2014.04.035

Cited by 41 publications

(51 citation statements)

References 46 publications

(41 reference statements)

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“…MDSC Adoptive Transfer-Adoptive transfer of G-MDSCs or M-MDSCs was performed as described previously (43). Briefly, MDSC subsets were isolated from spleen of ATF3-KO or Dex-treated WT mice by flow cytometric sorting, followed by tail vein injection (3 ϫ 10 6 ) into WT recipients on days 1 and 3.…”

Section: Methodsmentioning

confidence: 99%

Glucocorticoid Induces Hepatic Steatosis by Inhibiting Activating Transcription Factor 3 (ATF3)/S100A9 Protein Signaling in Granulocytic Myeloid-derived Suppressor Cells

Liu

Wei

Shi

et al. 2016

Journal of Biological Chemistry

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Glucocorticoids (GCs) used as inflammation suppressors have harmful side effects, including induction of hepatic steatosis. The underlying mechanisms of GC-promoted dysregulation of lipid metabolism, however, are not fully understood. GCs could facilitate the accumulation of myeloid-derived suppressor cells (MDSC) in the liver of animals, and the potential role of MDSCs in GC-induced hepatic steatosis was therefore investigated in this study. We demonstrated that granulocytic (G)-MDSC accumulation mediated the effects of GCs on the fatty liver, in which activating transcription factor 3 (ATF3)/S100A9 signaling plays an important role. ATF3-deficient mice developed hepatic steatosis and displayed expansion of G-MDSCs in the liver and multiple immune organs, which shared high similarity with the phenotype observed in GC-treated wild-type littermates. Adoptive transfer of GC-induced or ATF3-deficient G-MDSCs promoted lipid accumulation in the liver, whereas depletion of G-MDSCs alleviated these effects. Mechanistic studies showed that in MDSCs, ATF3 was transrepressed by the GC receptor GR through direct binding to the negative GR-response element. S100A9 is the major transcriptional target of ATF3 in G-MDSCs. Silencing S100A9 clearly alleviated G-MDSCs expansion and hepatic steatosis caused by ATF3 deficiency or GC treatment. Our study uncovers an important role of G-MDSCs in GC-induced hepatic steatosis, in which ATF3 may have potential therapeutic implications.

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Section: Methodsmentioning

confidence: 99%

Glucocorticoid Induces Hepatic Steatosis by Inhibiting Activating Transcription Factor 3 (ATF3)/S100A9 Protein Signaling in Granulocytic Myeloid-derived Suppressor Cells

Liu

Wei

Shi

et al. 2016

Journal of Biological Chemistry

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“…Aspirin treatment dampened the accumulation of G-MDSCs in the inflamed lung accompanied by increased Th2 airway responses [113]. It has further been demonstrated that COX and its product, PGE 2 , play an important role in the regulation of activation and accumulation of MDSCs through PGE 2 and PGE 4 receptors [113,114]. MDSCs and IL-10 levels significantly increased and negatively correlated with IL-12 levels during the onset of asthma in both human and mice.…”

Section: Mdscs In Lung Diseasesmentioning

confidence: 98%

“…The chemokine CCL2 was found to recruit MDSCs into lung tissues in airway inflammation [112]. Aspirin treatment dampened the accumulation of G-MDSCs in the inflamed lung accompanied by increased Th2 airway responses [113]. It has further been demonstrated that COX and its product, PGE 2 , play an important role in the regulation of activation and accumulation of MDSCs through PGE 2 and PGE 4 receptors [113,114].…”

Section: Mdscs In Lung Diseasesmentioning

confidence: 99%

The emerging role of myeloid-derived suppressor cells in lung diseases

et al. 2016

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Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterised by their potential to control T-cell responses and to dampen inflammation. While the role of MDSCs in cancer has been studied in depth, our understanding of their relevance for infectious and inflammatory disease conditions has just begun to evolve. Recent studies highlight an emerging and complex role for MDSCs in pulmonary diseases. In this review, we discuss the potential contribution of MDSCs as biomarkers and therapeutic targets in lung diseases, particularly lung cancer, tuberculosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis. @ERSpublications Myeloid-derived suppressor cells are involved in various lung diseases and represent promising therapeutic targets

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“…Quantitative real-time PCR analysis of transcripts was performed on Bio-Rad CFX96 real-time detection system using SYBR Green Master Mix (Applied Biosystems, Foster City, CA)5354. Relative mRNA expression levels were calculated after normalization to β-actin.…”

Section: Methodsmentioning

confidence: 99%

Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production

Yang

Xie

et al. 2016

Sci Rep

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Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor κB (NF-κB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1β could trigger NO production in MSCs and exert anti-mycobacterial activity via NF-κB signaling pathway. Neutralization of interleukin-1β in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection.

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Myeloid-derived suppressor cell function is diminished in aspirin-triggered allergic airway hyperresponsiveness in mice

Cited by 41 publications

References 46 publications

Glucocorticoid Induces Hepatic Steatosis by Inhibiting Activating Transcription Factor 3 (ATF3)/S100A9 Protein Signaling in Granulocytic Myeloid-derived Suppressor Cells

Glucocorticoid Induces Hepatic Steatosis by Inhibiting Activating Transcription Factor 3 (ATF3)/S100A9 Protein Signaling in Granulocytic Myeloid-derived Suppressor Cells

The emerging role of myeloid-derived suppressor cells in lung diseases

Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production

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