Chronic Psychological Stress Induces the Accumulation of Myeloid-Derived Suppressor Cells in Mice

Jin, Jianfeng; Wang, Xiaoqian; Wang, Qingyang; Guo, Xiuli; Cao, Jinglin; Zhang, Xueying; Zhu, Ting; Zhang, Dalin; Wang, Wendie; Wang, Jing; Shen, Beifen; Gao, Xu; Shi, Yuting; Zhang, Jiyan

doi:10.1371/journal.pone.0074497

Cited by 45 publications

(36 citation statements)

References 40 publications

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“…However, new data suggests that stress alone can lead to the accumulation of MDSCs, which are broadly defined as CD11b + GR1 + cells. Jin et al demonstrated that these cells have the potential to suppress immunity by producing factors such as nitric oxide and arginase [84]. These studies are in agreement with others showing a strong correlation between stress and immune suppression in breast cancer patients [85].…”

Section: Stress and Immunosuppressionsupporting

confidence: 82%

A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response

Eng

Kokolus

Reed

et al. 2014

Cancer Immunol Immunother

133

102

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Long conserved mechanisms maintain homeostasis in living creatures in response to a variety of stresses. However, continuous exposure to stress can result in unabated production of stress hormones, especially catecholamines, which can have detrimental health effects. While the long-term effects of chronic stress have well known physiological consequences, recent discoveries have revealed that stress may affect therapeutic efficacy in cancer. Growing epidemiological evidence reveals strong correlations between long term survival and cancer progression and β-blocker usage in patients. In this review, we summarize the current understanding of how the catecholamines, epinephrine and norepinephrine, affect cancer cell survival and tumor progression. We also highlight new data exploring the potential contributions of stress on immunosuppression in the tumor microenvironment and the implications of these findings for the efficacy of immunotherapies.

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Section: Stress and Immunosuppressionsupporting

confidence: 82%

A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response

Eng

Kokolus

Reed

et al. 2014

Cancer Immunol Immunother

133

102

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“…Our data demonstrates that a single IV dose of MSCs shortly following injury reversed the BM dysfunction seen following LC/CS and resulted in an increase in both BM cellularity and HPC growth within the BM to levels observed in naïve animals. The role of MSCs on the BM microenvironment has been studied in the setting of co-transplantation with HPCs and in autoimmune diseases marked by chronic inflammation 17–19 . When MSCs are co-transplanted with HPCs at the time of BM transplantation, they enhance the speed of recovery and reduce the incidence of graft-versus host disease (GVHD) 17–18 .…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells reverse bone marrow dysfunction following injury and stress

Gore

Bible²,

Livingston³

et al. 2015

Journal of Trauma and Acute Care Surgery

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Background Bone marrow (BM) dysfunction following experimental lung contusion (LC) resolves in 7 days, however, if followed by chronic stress (CS) following, BM dysfunction is persistent. Mesenchymal stem cells (MSC) have protective immunomodulatory effects. We hypothesize that MSC can protect the BM against the deleterious effect of CS following LC. Methods Male Sprague-Dawley rats (n=6–7/group) underwent LC or LC/CS ± MSC injection. CS consisted of a daily 2-hour period of restraint with repositioning and alarming every 30 minutes to prevent habituation. A single intravenous dose of 5 × 106 MSC was given within ten minutes following LC. Animals were sacrificed at day seven and peripheral blood (PB) and BM were collected. Flow cytometry was used to assess hematopoietic progenitor cells (HPCs) mobilized to PB. Plasma G-CSF levels were measured by ELISA. BM cellularity and growth of BM HPC colonies (CFU-E, BFU-E, CFU-GEMM) were also evaluated. Results As previously reported, the addition of CS to LC resulted in a 32% decrease in BM cellularity, significant decreases in CFU-GEMM, BFU-E, and CFU-E and marked increase in HPC in the PB as compared naïve animals. The addition of MSC to LC/CS resulted in a 22% increase in BM cellularity and significant increases in CFU-GEMM, BFU-E, and CFU-E cultured from the BM. MSCs additionally reduced plasma G-CSF, prevented prolonged mobilization of HPC to PB, and restored colony growth to naïve levels. Conclusion Chronic stress following LC results in persistent BM dysfunction manifested by a significant decrease in cellularity, HPC colony growth, and increased G-CSF levels and HPC mobilization to the PB at seven days following injury. The addition of a single dose of MSCs following acute traumatic injury reverses the deleterious effects of CS on BM function. Further study is warranted to better understand the mechanisms behind MSC-mediated protection of BM function in the setting of CS.

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“…In fact, there are very few studies demonstrating myelopoiesis in chronic stress models outside of RSD, whereas certain models reduce microbial activity. For example, several studies investigated the immune response to chronic restraint stress and reported diminished natural killer (NK) cell function, cytokine secretion, and enhanced viral replication (Hunzeker, Padgett et al 2004, Tseng, Padgett et al 2005, Jin, Wang et al 2013.…”

Section: Rsd-responsive Neuroendocrine Pathways Alter Homeostatic Hemmentioning

confidence: 99%

Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal

Weber

Godbout

Sheridan

2016

Neuropsychopharmacol

226

159

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Mounting evidence indicates that proinflammatory signaling in the brain affects mood, cognition, and behavior and is linked with the etiology of psychiatric disorders, including anxiety and depression. The purpose of this review is to focus on stress-induced bidirectional communication pathways between the central nervous system (CNS) and peripheral immune system that converge to promote a heightened neuroinflammatory environment. These communication pathways involve sympathetic outflow from the brain to the peripheral immune system that biases hematopoietic stem cells to differentiate into a glucocorticoid-resistant and primed myeloid lineage immune cell. In conjunction, microglia-dependent neuroinflammatory events promote myeloid cell trafficking to the brain that reinforces stress-related behavior, and is argued to play a role in stress-related psychiatric disorders. We will discuss evidence implicating a key role for endothelial cells that comprise the blood-brain barrier in propagating peripheral-to-central immune communication. We will also discuss novel neuron-to-glia communication pathways involving endogenous danger signals that have recently been argued to facilitate neuroinflammation under various conditions, including stress. These findings help elucidate the complex communication that occurs in response to stress and highlight novel therapeutic targets against the development of stress-related psychiatric disorders.

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Chronic Psychological Stress Induces the Accumulation of Myeloid-Derived Suppressor Cells in Mice

Cited by 45 publications

References 40 publications

A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response

A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response

Mesenchymal stem cells reverse bone marrow dysfunction following injury and stress

Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal

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