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Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [bulk RNA-seq]

ABSTRACT: The nervous and immune systems are intricately linked. Although psychological stress is known to affect immune function, direct mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood. Here, we show that distinct brain regions shape leukocyte distribution throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that the motor cortex induces rapid neutrophil mobilization to peripheral tissues via skeletal muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow via direct and cell-intrinsic glucocorticoid signaling. These stress-induced counter-directional and population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and precipitating their recruitment to atherosclerotic plaques. On the other hand, stress-induced leukocyte shifts impair adaptive immunity, increasing susceptibility to SARS-Cov-2 and influenza infection but protecting against autoimmunity in a model of multiple sclerosis. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, thus calibrating the immune system’s capacity to respond to physical threats.

ORGANISM(S): Mus musculus

PROVIDER: GSE201390 | GEO | 2022/04/28

REPOSITORIES: GEO

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Project description:Individual differences in basal leukocyte gene expression profiles as a function of child's and parent's perception of family stress, and as a function of parent's psychological well-being. Gene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 273 individuals (129 parent:child pairs + 15 parent-or-child) who were also assessed on their perceptions of family stress (both parent's and child's perception). Each dyad is labeled by a case ID, with p suffix indicating parent's gene expression profile and c suffix indicating child's gene expression profile. Variations in gene expression are analyzed as a function of both parent's perception of family stress and child's perception of family stress (using UCLA Life Stress Interview, as previously described: Hammen C (1991) Generation of stress in the course of unipolar depression. J Abnorm Psychol 100:555-561; Adrian C, Hammen C (1993) Stress Exposure and Stress Generation in Children of Depressed Mothers. Journal of Consulting and Clinical Psychology 61:354-359; Rudolph KD, Hammen C (1999) Age and gender as determinants of stress exposure, generation, and reactions in youngsters: A transactional perspective. Child Development 70:660-677). Higher values indicate greater levels of subjectively perceived family stress. Additional data are available for 107 parents who completed all 6 subscales of the Psychological Well-Being (PWB) Scale (Ryff CD (1989) Happiness is everything, or is it? Explorations on the meaning of psychological well-being. J. Pers Soc. Psychol 57: 1069-1081), resulting in scores for PWB_Total (average score across all 6 subscales) as well as scores for subscales measuring Purpose in Life (PWB_Purpose), Environmental Mastery (PWB_Environmental_Mastery), Self-Acceptance (PWB_Self_Accept), Autonomy (PWB_Autonomy), Personal Growth (PWB_Growth), Positive Relations with Others (PWB_Relationship). Higher scores indicate greater psychological well being. Also available for those individuals are measures of age (years), male gender (0/1), ethnic group (1=White, 2=Chinese, 3=Indian, 4=Other Asian, 5=Other Ethnicity), Body Mass Index (kg/m^2), heavy alcohol consumption history (0/1), smoking history (0/1), and abundance of 8 mRNA transcripts indicating the relative prevalence of major leukocyte subsets (CD3E, CD3D, CD19, CD4, CD8A, FCGR3A, NCAM1, CD14). key word: Risk prediction

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Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [bulk RNA-seq]

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