The brain–immune cells axis controls tissue specific immunopathology

Heyner, Maxi; Schreier, Sarah; Kröger, Andrea

doi:10.1038/s41423-018-0176-y

Cited by 6 publications

(5 citation statements)

References 7 publications

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“…Other factors in the TME can also regulate the expression level of PD-1. IL-7, IL-15 and IL-21 can induce the activation of PD-1 in peripheral T lymphocytes [ 74 ]. Although upregulated PD-1 does not affect the expansion and survival of T cells, it inhibits the secretion of cytokines [ 75 ].…”

Section: The Pd-1/pd-l1 Pathway In Cancer Immunotherapymentioning

confidence: 99%

Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation

et al. 2022

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Immune checkpoint molecules are promising anticancer targets, among which therapeutic antibodies targeting the PD-1/PD-L1 pathway have been widely applied to cancer treatment in clinical practice and have great potential. However, this treatment is greatly limited by its low response rates in certain cancers, lack of known biomarkers, immune-related toxicity, innate and acquired drug resistance, etc. Overcoming these limitations would significantly expand the anticancer applications of PD-1/PD-L1 blockade and improve the response rate and survival time of cancer patients. In the present review, we first illustrate the biological mechanisms of the PD-1/PD-L1 immune checkpoints and their role in the healthy immune system as well as in the tumor microenvironment (TME). The PD-1/PD-L1 pathway inhibits the anticancer effect of T cells in the TME, which in turn regulates the expression levels of PD-1 and PD-L1 through multiple mechanisms. Several strategies have been proposed to solve the limitations of anti-PD-1/PD-L1 treatment, including combination therapy with other standard treatments, such as chemotherapy, radiotherapy, targeted therapy, anti-angiogenic therapy, other immunotherapies and even diet control. Downregulation of PD-L1 expression in the TME via pharmacological or gene regulation methods improves the efficacy of anti-PD-1/PD-L1 treatment. Surprisingly, recent preclinical studies have shown that upregulation of PD-L1 in the TME also improves the response and efficacy of immune checkpoint blockade. Immunotherapy is a promising anticancer strategy that provides novel insight into clinical applications. This review aims to guide the development of more effective and less toxic anti-PD-1/PD-L1 immunotherapies.

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Section: The Pd-1/pd-l1 Pathway In Cancer Immunotherapymentioning

confidence: 99%

Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation

et al. 2022

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“…The HPA axis and adrenal steroid hormones such as GCs are essential regulators of the immune response suppressing inflammation. While lower adult GC levels and a blunted CORT response to stress have repeatedly been associated with early life stress 28 , 62 , a short term increase of GCs is tightly associated with viral infections and inflammation 63 . We hypothesized that hypercortisolemia would have a similar long-term effect early when induced by an early-life infection.…”

Section: Discussionmentioning

confidence: 99%

Early-life influenza A (H1N1) infection independently programs brain connectivity, HPA AXIS and tissue-specific gene expression profiles

Merz,

Seal,

Grova

et al. 2024

Sci Rep

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Early-life adversity covers a range of physical, social and environmental stressors. Acute viral infections in early life are a major source of such adversity and have been associated with a broad spectrum of later-life effects outside the immune system or “off-target”. These include an altered hypothalamus–pituitary–adrenal (HPA) axis and metabolic reactions. Here, we used a murine post-natal day 14 (PND 14) Influenza A (H1N1) infection model and applied a semi-holistic approach including phenotypic measurements, gene expression arrays and diffusion neuroimaging techniques to investigate HPA axis dysregulation, energy metabolism and brain connectivity. By PND 56 the H1N1 infection had been resolved, and there was no residual gene expression signature of immune cell infiltration into the liver, adrenal gland or brain tissues examined nor of immune-related signalling. A resolved early-life H1N1 infection had sex-specific effects. We observed retarded growth of males and altered pre-stress (baseline) blood glucose and corticosterone levels at PND42 after the infection was resolved. Cerebral MRI scans identified reduced connectivity in the cortex, midbrain and cerebellum that were accompanied by tissue-specific gene expression signatures. Gene set enrichment analysis confirmed that these were tissue-specific changes with few common pathways. Early-life infection independently affected each of the systems and this was independent of HPA axis or immune perturbations.

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“…In contrast, our results show that a higher level of serum cortisol is a positive predictive factor for COBMINDEX success in CD patients, as it predicts improvement in general health (low delta of GSI score). Since activating the HPA axis is known to induce a dynamic range of cortisol response ( Heyner et al., 2019 ), higher levels of circulating cortisol indicate that these individuals may be in a tense distress episode and thus are more likely to benefit from COBMINDEX ( Ince et al., 2019 ; Mikocka-Walus et al., 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…Usually, cortisol exerts major suppressive effects on the immune system by reducing the activity of circulating inflammatory cells and inhibiting the production of proinflammatory mediators ( Reed and Raison, 2016 ; Rea et al., 2017 ). Additionally, cortisol engenders negative feedback to the HPA axis to ultimately turn down or turn off the axis ( Heyner et al., 2019 ). Whereas the daily circadian rhythm of cortisol regulates inflammation, chronic stress may alter the response of cells to cortisol, producing the so-called steroid resistance ( Chavan et al., 2017 ; Ince et al., 2019 ), a process facilitating chronic inflammation and reducing the efficacy of corticosteroid drugs ( Harpaz et al., 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Brain-immune axis regulation is responsive to cognitive behavioral therapy and mindfulness intervention: Observations from a randomized controlled trial in patients with Crohn's disease

Nemirovsky

Ilan

Lerner

et al. 2022

Brain, Behavior, & Immunity - Health

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Background and aims Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the hypothalamus-pituitary-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) impacts their inflammatory process. Methods Circulating inflammatory markers and a wide range of psychological parameters related to stress and well-being were measured in CD patients before and after COBMINDEX. Inflammatory markers in CD patients were also compared to age- and sex-matched healthy controls (HCs). Results CD patients exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by interconnected inflammatory modules represented by IL-6, TNFα, IL-17, MCP-1 and IL-18. Notably, higher IL-18 levels correlated with higher score of stress and a lower score of wellbeing in CD patients. COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 and IFNα and negatively with those of MCP-1. Furthermore, inflammatory markers of CD patients at baseline predicted COBMINDEX efficacy, as higher levels of distinct cytokines and cortisol at baseline, correlated negatively with changes in disease activity (by Harvey-Bradshaw Index) and psychological distress (global severity index measure) following COBMINDEX. Conclusion CD patients have a characteristic immunological profile that correlates with psychological stress, and disease severity. We suggest that COBMINDEX induces stress resilience in CD patients, which impacts their well-being, and their disease-associated inflammatory process.

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The brain–immune cells axis controls tissue specific immunopathology

Cited by 6 publications

References 7 publications

Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation

Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation

Early-life influenza A (H1N1) infection independently programs brain connectivity, HPA AXIS and tissue-specific gene expression profiles

Brain-immune axis regulation is responsive to cognitive behavioral therapy and mindfulness intervention: Observations from a randomized controlled trial in patients with Crohn's disease

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