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      The neuroimmune response during stress- a physiological perspective

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      Immunity

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          Summary

          Stress is an essential adaptive response that enables the organism to cope with challenges and restore homeostasis. Different stressors require distinctive corrective responses in which immune cells play a critical role. Hence, effects of stress on immunity should vary depending on the stressor. Indeed, epidemiologically, stress can induce either inflammation or immune suppression. However, in the absence of a conceptual framework, these effects appear chaotic, leading to confusion. Here, we examine how stressor diversity is imbedded in the neuroimmune axis. Stressors differ in the brain patterns they induce, diversifying the neuronal and endocrine mediators dispatched to the periphery generating a range of potential immune effects. Uncovering this complexity and diversity of immune responses to stressors will allow us to understand the involvement of stress in pathological conditions, identify ways to modulate it, and even harness the therapeutic potential embedded in an adaptive stress response.

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          Most cited references152

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          Stress and the individual. Mechanisms leading to disease.

          This article presents a new formulation of the relationship between stress and the processes leading to disease. It emphasizes the hidden cost of chronic stress to the body over long time periods, which act as a predisposing factor for the effects of acute, stressful life events. It also presents a model showing how individual differences in the susceptibility to stress are tied to individual behavioral responses to environmental challenges that are coupled to physiologic and pathophysiologic responses. Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE. Independent extraction and cross-referencing by us. Stress is frequently seen as a significant contributor to disease, and clinical evidence is mounting for specific effects of stress on immune and cardiovascular systems. Yet, until recently, aspects of stress that precipitate disease have been obscure. The concept of homeostasis has failed to help us understand the hidden toll of chronic stress on the body. Rather than maintaining constancy, the physiologic systems within the body fluctuate to meet demands from external forces, a state termed allostasis. In this article, we extend the concept of allostasis over the dimension of time and we define allostatic load as the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful. This new formulation emphasizes the cascading relationships, beginning early in life, between environmental factors and genetic predispositions that lead to large individual differences in susceptibility to stress and, in some cases, to disease. There are now empirical studies based on this formulation, as well as new insights into mechanisms involving specific changes in neural, neuroendocrine, and immune systems. The practical implications of this formulation for clinical practice and further research are discussed.
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            Immune regulation by glucocorticoids

            In this Review, the authors discuss the effects of glucocorticoids on both innate and adaptive immunity. They explain the mechanistic basis of glucocorticoid-mediated immunosuppression and highlight the less well-appreciated roles of glucocorticoids in enhancing immune responses.
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              Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner

              Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2 + lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.
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                Author and article information

                Journal
                9432918
                Immunity
                Immunity
                Immunity
                1074-7613
                1097-4180
                14 September 2021
                22 November 2023
                07 December 2023
                : 54
                : 9
                : 1933-1947
                Affiliations
                Department of immunology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, 3525422, Israel
                Author notes
                Corresponding author: Asya Rolls; rolls@ 123456technion.ac.il
                Article
                EMS191483
                10.1016/j.immuni.2021.08.023
                7615352
                34525336
                fe4f41c4-b925-433b-a7f8-d14c69b3b90d

                This work is licensed under a BY 4.0 International license.

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                Immunology
                Immunology

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