Faculty Opinions recommendation of The effects of early life adversity on the immune system.

2017 ◽  
Author(s):  
Robert Strecker ◽  
Mark Zielinski
Keyword(s):  
Immune System ◽  
Early Life ◽  
Early Life Adversity

scholarly journals Effects of early life adversity on meningeal mast cells and proinflammatory gene expression in male and female Mus musculus

2021 ◽  
Author(s):  
Natalia Duque-Wilckens ◽  
Erika Sarno ◽  
Robby E. Teis ◽  
Frauke Stoelting ◽  
Sonia Khalid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mast Cell ◽  
Immune System ◽  
Mast Cells ◽  
Early Life ◽  
Inflammatory Markers ◽  
Disease Susceptibility ◽  
Early Life Adversity ◽  
Male And Female ◽  
The Brain

ABSTRACTExposure to early life adversity (ELA) in the form of physical and/or psychological abuse or neglect increases the risk of developing psychiatric and inflammatory disorders later in life. It has been hypothesized that exposure to ELA results in persistent, low grade inflammation that leads to increased disease susceptibility by amplifying the crosstalk between stress-processing brain networks and the immune system, but the mechanisms remain largely unexplored. The meninges, a layer of three overlapping membranes that surround the central nervous system (CNS)- duramater, arachnoid, and piamater – possess unique features that allow them to play a key role in coordinating immune trafficking between the brain and the peripheral immune system. These include a network of lymphatic vessels that carry cerebrospinal fluid from the brain to the deep cervical lymph nodes, fenestrated blood vessels that allow the passage of molecules from blood to the CNS, and a rich population of resident mast cells, master regulators of the immune system. Using a mouse model of ELA consisting of neonatal maternal separation plus early weaning (NMSEW), we sought to explore the effects of ELA on duramater mast cell histology and expression of inflammatory markers in male and female C57Bl/6 mice. We found that mast cell number, activation level, and relative expression of pseudopodia differ across duramater regions, and that NMSEW exerts region-specific effects on mast cells in males and females. Using gene expression analyses, we next found that NMSEW increases the expression of inflammatory markers in the duramater of females but not males, and that this is prevented by pharmacological inhibition of mast cells with ketotifen. Together, our results show that ELA drives sex-specific, long-lasting effects on the duramater mast cell population and immune-related gene expression, suggesting that the long-lasting effects of ELA on disease susceptibility could be partly mediated by meningeal function.

Glucocorticoid receptor signaling in leukocytes after early life adversity

2019 ◽  
Vol 32 (3) ◽  
pp. 853-863 ◽  
Author(s):  
Martha M. C. Elwenspoek ◽  
Xenia Hengesch ◽  
Fleur A. D. Leenen ◽  
Krystel Sias ◽  
Sara Beatriz Fernandes ◽  
...  
Keyword(s):  
Immune System ◽  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Early Life ◽  
Promoter Region ◽  
Target Genes ◽  
Early Life Adversity ◽  
Time Points ◽  
Biological Parents ◽  
Separation From Parents

AbstractEarly life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA.Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.

Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psycho-Social Stress

2021 ◽  
Author(s):  
Sara B. Fernandes ◽  
Neha D. Patil ◽  
Sophie B. Meriaux ◽  
Maud Theresine ◽  
Fleur A.D. Leenen ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Nk Cells ◽  
Early Life ◽  
Social Stress ◽  
Maternal Separation ◽  
Economic Status ◽  
Childhood Adversity ◽  
Early Life Adversity ◽  
Human Situation

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD), the closest animal model available to the human situation, is known to similarly induce long lasting behavioural effects, to cause changes in the HPA axis and to have an impact in the immune system. Even though the immune responses to potential pathogens after early stress have been somehow documented, the mechanisms by which they occur are still not fully understood. Here, we have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after childhood adversity. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. Altogether, these results lead us to conclude that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

scholarly journals Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psychosocial Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Sara B. Fernandes ◽  
Neha D. Patil ◽  
Sophie Meriaux ◽  
Maud Theresine ◽  
Claude. P. Muller ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Early Life ◽  
Maternal Separation ◽  
Immune Cell ◽  
Economic Status ◽  
Immune Cell Population ◽  
Early Life Adversity ◽  
Social Economic Status ◽  
Human Situation

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD) is the closest animal model available to the human situation. This paradigm induces long lasting behavioral effects, causes changes in the HPA axis and affects the immune system. However, the mechanisms underlying changes in the immune response after ELA are still not fully understood. In this study we investigated how ELA changes the immune system, through an unbiased analysis, viSNE, and addressed specially the NK immune cell population and its functionality. We have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after ELA. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. These results suggest that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

The effects of early life adversity on the immune system

2017 ◽  
Vol 82 ◽  
pp. 140-154 ◽  
Author(s):  
Martha M.C. Elwenspoek ◽  
Annette Kuehn ◽  
Claude P. Muller ◽  
Jonathan D. Turner
Keyword(s):  
Immune System ◽  
Early Life ◽  
Early Life Adversity

Resilience in Adolescence: Prospective Self Moderates the Association of Early Life Adversity with Psychopathology

2019 ◽  
Author(s):  
Mary Elizabeth Zinn ◽  
Edward Huntley ◽  
Daniel Keating
Keyword(s):  
Behavior Problems ◽  
Identity Formation ◽  
Externalizing Behavior ◽  
Early Life ◽  
The United States ◽  
Externalizing Behavior Problems ◽  
Developmental Period ◽  
Equation Modeling ◽  
Early Life Adversity ◽  
Latent Construct

Introduction. Early life adversity (ELA) can result in negative health-outcomes, including psychopathology. Evidence suggests that adolescence is a critical developmental period for processing ELA. Identity formation, which is crucial to this developmental period, may moderate the effect between ELA and psychopathology. One potential moderating variable associated with identity formation is Prospective Self, a latent construct comprised of future-oriented attitudes and behaviors.Methods. Participants are from the first wave of an ongoing longitudinal study designed to characterize behavioral and cognitive correlates of risk behavior trajectories. A community sample of 10th and 12th grade adolescents (N = 2017, 55% female) were recruited from nine public school districts across eight Southeastern Michigan counties in the United States. Data were collected in schools during school hours or after school via self-report, computer-administered surveys. Structural equation modeling was used in the present study to assess Prospective Self as a latent construct and to evaluate the relationship between ELA, psychopathology, and Prospective Self.Results. Preliminary findings indicated a satisfactory fit for the construct Prospective Self. The predicted negative associations between Prospective Self and psychopathology were found and evidence of moderation was observed for externalizing behavior problems, such that the effects of ELA were lower for individuals with higher levels of Prospective Self. Conclusion. These results support the role of Prospective Self in conferring resilience against externalizing behavior problems associated with ELA among adolescents. Keywords: Adolescence, Adverse Childhood Experiences, Psychopathology, Self-concept, Adolescent Health, Early Life Adversity

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