Decrease of CD4+FOXP3+ T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor

Freier, Eva; Weber, Cora; Nowottne, Ulrike; Horn, Clemens R.; Bartels, Katrin; Meyer, Scott C.; Hildebrandt, York; Luetkens, Tim; Cao, Yanran; Pabst, Caroline; Muzzulini, Julia; Schnee, Benjamin; Brunner‐Weinzierl, Monika C.; Marangolo, M.; Bokemeyer, Carsten; Deter, Hans‐Christian; Atanackovic, Djordje

doi:10.1016/j.psyneuen.2009.10.005

Cited by 65 publications

(48 citation statements)

References 51 publications

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“…Psychosocial stress decreases Treg in mice and humans (50,51), and Treg depletion increases anxiety-and depressive-like behaviors in mice (52). Likewise, PTSD subjects (9) and subjects with major depressive disorder (53) have reduced Treg, which is reversed 1 y following effective narrative exposure therapy (54) or treatment with antidepressants, respectively (53).…”

Section: Persistent Effects Of M Vaccae Immunization On Brain Serotomentioning

confidence: 99%

Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice

Reber

Siebler

Donner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

199

153

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The prevalence of inflammatory diseases is increasing in modern urban societies. Inflammation increases risk of stress-related pathology; consequently, immunoregulatory or antiinflammatory approaches may protect against negative stress-related outcomes. We show that stress disrupts the homeostatic relationship between the microbiota and the host, resulting in exaggerated inflammation. Repeated immunization with a heat-killed preparation of Mycobacterium vaccae, an immunoregulatory environmental microorganism, reduced subordinate, flight, and avoiding behavioral responses to a dominant aggressor in a murine model of chronic psychosocial stress when tested 1-2 wk following the final immunization. Furthermore, immunization with M. vaccae prevented stress-induced spontaneous colitis and, in stressed mice, induced anxiolytic or fear-reducing effects as measured on the elevated plus-maze, despite stress-induced gut microbiota changes characteristic of gut infection and colitis. Immunization with M. vaccae also prevented stress-induced aggravation of colitis in a model of inflammatory bowel disease. Depletion of regulatory T cells negated protective effects of immunization with M. vaccae on stress-induced colitis and anxiety-like or fear behaviors. These data provide a framework for developing microbiome-and immunoregulation-based strategies for prevention of stress-related pathologies.anxiety | chronic psychosocial stress | fear | microbiota | posttraumatic stress disorder

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Section: Persistent Effects Of M Vaccae Immunization On Brain Serotomentioning

confidence: 99%

Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice

Reber

Siebler

Donner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

199

153

View full text Add to dashboard Cite

show abstract

“…This indicates that high-stressed children have a low spontaneous activity of Th2, Tr1, and Th17 cells, which suggests a suppressive immune response. Several studies have shown that stress exposure is associated with impaired cell-mediated acquired immunity (20,(34)(35)(36)(37)(38)(39). In 2010, Freier et al (20) showed that Tregs are downregulated during stress and concluded that this might result in an exacerbation of inflammatory conditions such as an autoimmune condition.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that stress exposure is associated with impaired cell-mediated acquired immunity (20,(34)(35)(36)(37)(38)(39). In 2010, Freier et al (20) showed that Tregs are downregulated during stress and concluded that this might result in an exacerbation of inflammatory conditions such as an autoimmune condition. Further, a recent study showed that chronic exposure to stress shifts the Th1/Th2 balance toward a proinflammatory Th1/Th17 dominance versus Th2 response and also downregulates Tregs in mice (40).…”

Section: Discussionmentioning

confidence: 99%

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Psychological Stress in Children May Alter the Immune Response

Carlsson

Frostell

Ludvigsson

et al. 2014

The Journal of Immunology

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Psychological stress is a public health issue even in children and has been associated with a number of immunological diseases. The aim of this study was to examine the relationship between psychological stress and immune response in healthy children, with special focus on autoimmunity. In this study, psychological stress was based on a composite measure of stress in the family across the domains: 1) serious life events, 2) parenting stress, 3) lack of social support, and 4) parental worries. PBMCs, collected from 5-y-old high-stressed children (n = 26) and from 5-y-old children without high stress within the family (n = 52), from the All Babies In Southeast Sweden cohort, were stimulated with Ags (tetanus toxoid and β-lactoglobulin) and diabetes-related autoantigens (glutamic acid decarboxylase 65, insulin, heat shock protein 60, and tyrosine phosphatase). Immune markers (cytokines and chemokines), clinical parameters (C-peptide, proinsulin, glucose), and cortisol, as an indicator of stress, were analyzed. Children from families with high psychological stress showed a low spontaneous immune activity (IL-5, IL-10, IL-13, IL-17, CCL2, CCL3, and CXCL10; p < 0.01) but an increased immune response to tetanus toxoid, β-lactoglobulin, and the autoantigens glutamic acid decarboxylase 65, heat shock protein 60, and tyrosine phosphatase (IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, CCL2, CCL3, and CXCL10; p < 0.05). Children within the high-stress group showed high level of cortisol, but low level of C-peptide, compared with the control group (p < 0.05). This supports the hypothesis that psychological stress may contribute to an imbalance in the immune response but also to a pathological effect on the insulin-producing β cells.

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“…Indeed, convincing evidence suggests that it is possible for CAs (stress) to affect Tregs in in vivo environment and in ex vivo cultures (22,34,35). The effects of CAs on Tregs are achieved through both indirect and direct mechanisms.…”

Section: The Journal Of Immunologymentioning

confidence: 99%

Propranolol Attenuates Surgical Stress–Induced Elevation of the Regulatory T Cell Response in Patients Undergoing Radical Mastectomy

Zhou

et al. 2016

The Journal of Immunology

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Surgical stress and inflammatory response induce the release of catecholamines and PGs, which may be key factors in facilitating cancer recurrence through immunosuppression. Animal studies have suggested the efficacy of perioperative blockades of catecholamines and PGs in reducing immunosuppression. In this study, to our knowledge, we present the first report of the effects of perioperative propranolol and/or parecoxib on peripheral regulatory T cells (Tregs) in breast cancer patients. Patients were randomly assigned to control, propranolol, parecoxib, and propranolol plus parecoxib groups. We demonstrated that levels of circulating epinephrine, norepinephrine, and PGE2 increased in response to surgery. Meanwhile, peripheral FOXP3 mRNA level and Treg frequencies were elevated on postoperative day 7. Propranolol administration, rather than parecoxib, attenuated such elevation of Tregs, indicating the critical roles for catecholamines in surgery-induced promotion of Tregs. Besides, propranolol plus parecoxib treatment demonstrated no additive or synergistic effects. Furthermore, a study of Treg activity on CD4+ T cell responses to specific tumor Ags was performed in the control and propranolol groups. Propranolol abrogated the increased Treg activity and accompanying suppression of CD4+ T cell responses after surgery. Finally, we conducted ex vivo experiments on the effects of varying concentrations of epinephrine and/or propranolol on Treg proliferation over PBMCs from breast cancer patients, to provide further direct evidence strengthening our clinical observations. Epinephrine markedly promoted Treg proliferation, whereas propranolol prevented such enhancement effect. In conclusion, our study highlights beneficial roles for propranolol in inhibiting Treg responses in vivo and in vitro, and demonstrates that propranolol could alleviate surgical stress–induced elevation of Tregs in breast cancer patients.

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Decrease of CD4+FOXP3+ T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor

Cited by 65 publications

References 51 publications

Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice

Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice

Psychological Stress in Children May Alter the Immune Response

Propranolol Attenuates Surgical Stress–Induced Elevation of the Regulatory T Cell Response in Patients Undergoing Radical Mastectomy

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