Circulating Myeloid-Derived Suppressor Cells Are Increased and Activated in Pulmonary Hypertension

Yeager, Michael E.; Nguyen, Cecilia M.; Belchenko, Dmitry; Colvin, Kelley L.; Takatsuki, Shinichi; Ivy, D. Dunbar; Stenmark, Kurt R.

doi:10.1378/chest.11-0205

Cited by 38 publications

(38 citation statements)

References 39 publications

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“…The dramatic expansion of the CD14 + HLA-DR -/low MDSC population in response to ACS is very similar to that previously described in patients with other inflammatory diseases [13,29,30,31]. Although the direct mechanism of MDSC generation has not been fully elucidated, several lines of evidence offer clues as to how the high frequency of circulating MDSCs might occur in the context of ACS.…”

Section: Discussionsupporting

confidence: 79%

“…Although the role of MDSCs in cancer has been intensively explored, additional work also implicates MDSCs in the pathogenesis of chronic inflammatory and autoimmune diseases, including inflammatory bowel disease [29], viral infection-related diseases [13], rheumatoid arthritis [30], and pulmonary hypertension [31]. However, little is known about the role of MDSCs in patients with ACS.…”

Section: Introductionmentioning

confidence: 99%

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Expansion of Myeloid-Derived Suppressor Cells in Patients with Acute Coronary Syndrome

Wang

Xiong

Chen

et al. 2015

Cell Physiol Biochem

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Aim: The aim of this study was to explore whether the circulating frequency and function of myeloid-derived suppressor cells (MDSCs) are altered in patients with acute coronary syndrome (ACS). Methods: The frequency of MDSCs in peripheral blood was determined by flow cytometry, and mRNA expression in purified MDSCs was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The suppressive function of MDSCs isolated from different groups was also determined. The plasma levels of certain cytokines were determined using Bio-Plex Pro™ Human Cytokine Assays. Results: The frequency of circulating CD14⁺HLA-DR^-/low MDSCs; arginase-1 (Arg-1) expression; and plasma levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-33 were markedly increased in ACS patients compared to stable angina (SA) or control patients. Furthermore, MDSCs from ACS patients were more potent suppressors of T-cell proliferation and IFN-γ production than those from the SA or control groups at ratios of 1:4 and 1:2; this effect was partially mediated by Arg-1. In addition, the frequency of MDSCs was positively correlated with plasma levels of IL-6, IL-33, and TNF-α. Conclusions: We observed an increased frequency and suppressive function of MDSCs in ACS patients, a result that may provide insights into the mechanisms involved in ACS.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Expansion of Myeloid-Derived Suppressor Cells in Patients with Acute Coronary Syndrome

Wang

Xiong

Chen

et al. 2015

Cell Physiol Biochem

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“…In this respect, abnormalities of T lymphocyte subsets have been documented in patients with pulmonary hypertension [131,132]. In pulmonary hypertension patients, circulating activated MDSC numbers were significantly increased in comparison to control subjects and correlated with increasing mean pulmonary artery pressure [133]. A direct mechanistic role for MDSCs in pulmonary hypertension and inflammation-associated vascular remodelling has not yet been defined.…”

Section: Pulmonary Hypertensionmentioning

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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“…They found significant enrichment of circulating fibrocytes and a positive correlation (albeit weak) between PAP and age. With the knowledge of ongoing inflammation in PH in which the innate and adaptive immune systems have been implicated, Yeager et al also examined myeloidderived suppressor cells (MDSCs) [37], a subpopulation of which (monocyte-derived dendritic cells) was suggested to be functionally impaired in IPAH. Circulating MDSCs have been shown to be increased in human and animal PH lung.…”

Section: The Current State Of Ph Biomarkersmentioning

confidence: 99%

The untapped potential of proteomic analysis in pediatric pulmonary hypertension

Nies

Ivy

2014

Proteomics Clinical Apps

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Analysis of the human proteome has become increasingly sophisticated, and offers invaluable potential insight into the pathophysiology of human disease. The increasing standardization of methods, speed, and sophistication of mass spectrometric analysis, availability of reliable antibodies, and dissemination of information among the scientific community has allowed for exponential growth of our knowledge base. The continued effort to provide a molecular explanation for future medical applications based on biomarker discovery is epitomized by the outstanding efforts of the human proteome project, whose goal is to generate a map of the human proteome. However, proteomic analysis is underrepresented in pediatric illness; given the unique challenges of research in the pediatric population, proteomic analysis represents enormous untapped potential, especially in the further elucidation of the pathophysiology of rare diseases such as pulmonary hypertension (PH). In this article, we will describe the unique challenge of pediatric research, the importance of alternative avenues such as proteomics for in-depth analysis of pediatric pathobiology at the cellular level, the specific need for proteomic investigation of pediatric PH, the current status of PH proteomics, and future directions.

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Circulating Myeloid-Derived Suppressor Cells Are Increased and Activated in Pulmonary Hypertension

Cited by 38 publications

References 39 publications

Expansion of Myeloid-Derived Suppressor Cells in Patients with Acute Coronary Syndrome

Expansion of Myeloid-Derived Suppressor Cells in Patients with Acute Coronary Syndrome

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

The untapped potential of proteomic analysis in pediatric pulmonary hypertension

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