Accumulation of Myeloid-Derived Suppressor Cells: A New Mechanism in Favor of Stress-Induced Immunosuppression?
Jianfeng Jin et al. present a mechanism for the immunosuppressive potential of chronic stress in the September 2013 issue of PLoS One.
The authors focus on myeloid-derived suppressor cells (MDSCs), which have been implicated in regulation of the innate and adaptive immune responses. In tumor microenvironments, MDSC expansion is stimulated by prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF), and elevated MDSCs levels were noted in a case series of breast cancer patients undergoing life stressors.
Hence, the authors hypothesized that there may be a relationship between prolonged psychological stress and MDSCs. A mouse model using restraint as a chronic stressor was utilized, and bone marrow, spleen, and thymus were examined. The bone marrow and peripheral blood of stressed mice showed accumulation of CD11b+Gr1+ cells. PGE2 levels but not VEGF levels were found to be elevated, and catecholamines also appeared to play a role in MDSC accumulation, as β-adrenergic receptor blockade with propranolol partially reversed the noted accumulation.
As the biosynthetic pathway for PGE2 depends on the inducible cyclooxygenase 2 (COX-2) enzyme and catecholamines contribute to COX-2 induction under a pro-inflammatory environment, the authors suggest that the COX-2-PGE2 loop mediates the MDSCs accumulation downstream of catecholamines.
Of note, bone marrow CD11b+Gr1+ cells isolated from stressed mice produced more TNF-α upon LPS stimulation, but exhibited higher ability to induce the production of IL-10 in primary macrophages.
This study highlights the complex interplay between psychological stress and immunity and may reveal a new mechanism by which stress can induce immunosuppression.
Source: PLoS One. 2013, 8:e74497. doi: 10.1371/journal.pone.0074497. eCollection 2013.
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