Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis

In the citing paper

“Chronic stress mobilizes the innate immune system and stimulates enhanced proliferation and release of inflammatory monocytes and neutrophils into the bloodstream12, 13.”

In the citing paper

“In the context of metastatic breast cancer, for example, stress effects on tumor metastasis are mediated by β-adrenergic up-regulation of monocytes and macrophages within the tumor microenvironment [44] (i.e., the same dynamic that drives the CTRA transcriptome shift in circulating blood [9]).”

In the citing paper

“For example, research demonstrates social isolation modulates immune responses and induces inflammation [40,41].”

In the citing paper

“Powell et al. (2013) show that social stress causes inflammatory gene expression in 2-adrenergic pathways that involve the activation of the sympathetic nervous system.”

In the citing paper

“RSD causes rodents to release immature, pro-inflammatory immune cells (CD11b+/Ly6C high) into circulation that serve to promote inflammation at the site of injury (Powell et al., 2013).”

In the citing paper

“Following the initial analyses of social isolation, a diverse array of studies has begun to document similar leukocyte transcriptome shifts in other adverse social conditions, including low socioeconomic status (SES) [9], [17]–[20], chronic stress (e.g., care-giving for a dying spouse) [21], [22], bereavement [23], post-traumatic stress disorder (PTSD) [24], [25], and cancer diagnosis [26], [27].”

In the citing paper

“Subsequent studies using experimental animal models has shown that CTRA gene expression profiles can be induced in leukocytes by repeated social threat [9], unstable social hierarchies [8], [29], and low social status [7].”

In the citing paper

“Subsequent analysis of physically isolated leukocyte subpopulations confirmed that monocytes mediate many of the transcriptional effects of human social adversity [21], [25], and mechanistic analyses in animal models determined that the SNS can up-regulate the production of a distinct subpopulation of immature, proinflammatory monocytes by altering hematopoietic processes in the bone marrow [9].”

In the citing paper

“These effects are again mediated by β-adrenergic signaling, which up-regulates transcription of the myelopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) (Csf3) and thereby enhances monocyte differentiation and development [9].”

In the citing paper

“For example, RSD increases monocyte and granulocyte progenitor cells in the BM that traffic into circulation and are redistributed throughout the body (Engler et al, 2004;Powell et al, 2013).”

In the citing paper

“Chronic stressors or repeated exposure to social defeat shifts hematopoietic stem cell differentiation toward the myeloid cell lineage.”

In the citing paper

“Furthermore, treatment with a GM-CSF neutralizing antibody prevented RSD-induced expansion of granulocytes and monocytes.”

In the citing paper

“Furthermore, pharmacological blockage of the β-adrenergic receptor before RSD prevented BM-derived myeloid cell differentiation and redistribution in circulation (Wohleb et al, 2011;Hanke et al, 2012;Powell et al, 2013).”

In the citing paper

“Based on data from flow cytometry scatter properties, RSD preferentially increases the amount of circulating Ly6C hi monocytes (Powell et al, 2013;Wohleb et al, 2013;Ramirez et al, 2015a) that is prevented by blockage of the β-adrenergic receptor (Hanke et al, 2012;Powell et al, 2013).”

In the citing paper

“In support of this, genome-wide transcriptional profiling indicates that splenetic monocytes upregulate MMP 8/9/13/14 in response to RSD (Powell et al, 2013).”

In the citing paper

“Here, RSD increased the presence of CD11b + /CD45 high monocyte population in CNS (Wohleb et al, 2011).”

In the citing paper

“Further investigation revealed that the primary source of upregulated inflammatory genes among caretakers was derived from an increased CD14 + /CD16 -monocyte population (Powell et al, 2013;Miller et al, 2014).”