Genetic and epigenetic factors in the regulation of the immune response

Dahmer, Mary K.; Cornell, Timothy T.; Quasney, Michael W.

doi:10.1097/mop.0000000000000356

Cited by 7 publications

(5 citation statements)

References 76 publications

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“…Finally, epigenetic alterations are often implicated to contribute to incomplete penetrance and late-onset disease. Epigenetic modifications play an important role in shaping our immune system and response ( 28 , 29 ). This is demonstrated by the identification of genetic defects involved in methylation, histone modification, chromatin remodeling and alteration in non-coding RNA resulting in different immunodeficiency syndromes ( 29 ).…”

Section: Mechanisms Of Adult-onset Presentation In Monogenic Ieimentioning

confidence: 99%

Monogenic Adult-Onset Inborn Errors of Immunity

et al. 2021

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Inborn errors of immunity (IEI) are a heterogenous group of disorders driven by genetic defects that functionally impact the development and/or function of the innate and/or adaptive immune system. The majority of these disorders are thought to have polygenic background. However, the use of next-generation sequencing in patients with IEI has led to an increasing identification of monogenic causes, unravelling the exact pathophysiology of the disease and allowing the development of more targeted treatments. Monogenic IEI are not only seen in a pediatric population but also in adulthood, either due to the lack of awareness preventing childhood diagnosis or due to a delayed onset where (epi)genetic or environmental factors can play a role. In this review, we discuss the mechanisms accounting for adult-onset presentations and provide an overview of monogenic causes associated with adult-onset IEI.

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Section: Mechanisms Of Adult-onset Presentation In Monogenic Ieimentioning

confidence: 99%

Monogenic Adult-Onset Inborn Errors of Immunity

et al. 2021

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“…It seems therefore, that different inflammatory responses associated genes and proteins are up-regulated in the Majorera breed because of feed restriction. Considering the defense mechanisms pathway, gene SVEP1 is one of the various components of the immune response [44], whereas LOC102187241 codes for protein BPI fold containing family B member 1, a protein of inflammatory response in the upper airway and the progression of non-small cell lung cancer in humans [45]. Such results are difficult to interprete and further studies are needed to better understand these results.…”

Section: Major Pathways Affected By Weight Loss In the Majorera Mammamentioning

confidence: 99%

Understanding seasonal weight loss tolerance in dairy goats: a transcriptomics approach

et al. 2020

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Background Seasonal weight loss (SWL) is a very important limitation to the production of ruminants in the Mediterranean and Tropical regions. In these areas, long dry seasons lead to poor pastures with low nutritional value. During the dry season, ruminants, particularly those raised in extensive production systems, lose around 30% of their body weight. Seasonal weight loss has important consequences on animal productive performance and health. In this study, RNA sequencing was used to characterize feed restriction effects in dairy goat of 2 breeds with different SWL tolerance: Majorera (tolerant) and Palmera (susceptible). Nine Majorera and ten Palmera goats were randomly distributed in a control and a restricted group: Majorera Control (adequately fed; MC; n = 4), Palmera Control (adequately fed; PC; n = 6), Majorera Restricted (feed restricted; ME; n = 5) and Palmera Restricted (feed restricted; PE; n = 4). On day 22 of the trial, mammary gland biopsies were collected for transcriptomics analysis. Results From these samples, 24,260 unique transcripts were identified. From those, 82 transcripts were differentially expressed between MC and ME, 99 between PC and PE, twelve between both control groups and twenty-nine between both restricted groups. Conclusions Feed restriction affected several biochemical pathways in both breeds such as: carbohydrate and lipid transport; intracellular trafficking, RNA processing and signal transduction. This research also highlights the importance or involvement of the genes in tolerance (ENPP1, S-LZ, MT2A and GPNB) and susceptibility (GPD1, CTPS1, ELOVL6 and NR4A1) to SWL with respectively higher expression in the Majorera restriced group and the Palmera restricted group in comparison to the control groups. In addition, results from the study may be extrapolated to other dairy ruminant species.

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“…Increasing levels of PICs together with increasing levels of ROS and reactive nitrogen species (RNS) can induce further damage to tissues and macromolecules leading to increased DAMP formation and TLR engagement, ultimately producing higher levels of PICs and free radical species [36]. Increased levels of PICs ROS, RNS and NF-κB can also combine to drive a self-sustaining cellular environment of chronic inflammation and oxidative stress by modulating epigenetic mechanisms, notably DNA methylation and histone acetylation, responsible for governing the performance of immune and inflammatory pathways during and after activation, as we will now discuss [158, 159].…”

Section: Factors Involved In Influencing the Duration And Magnitude Omentioning

confidence: 99%

Socioeconomic Deprivation, Adverse Childhood Experiences and Medical Disorders in Adulthood: Mechanisms and Associations

et al. 2019

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Severe socioeconomic deprivation (SED) and adverse childhood experiences (ACE) are significantly associated with the development in adulthood of (i) enhanced inflammatory status and/or hypothalamic–pituitary–adrenal (HPA) axis dysfunction and (ii) neurological, neuroprogressive, inflammatory and autoimmune diseases. The mechanisms by which these associations take place are detailed. The two sets of consequences are themselves strongly associated, with the first set likely contributing to the second. Mechanisms enabling bidirectional communication between the immune system and the brain are described, including complex signalling pathways facilitated by factors at the level of immune cells. Also detailed are mechanisms underpinning the association between SED, ACE and the genesis of peripheral inflammation, including epigenetic changes to immune system-related gene expression. The duration and magnitude of inflammatory responses can be influenced by genetic factors, including single nucleotide polymorphisms, and by epigenetic factors, whereby pro-inflammatory cytokines, reactive oxygen species, reactive nitrogen species and nuclear factor-κB affect gene DNA methylation and histone acetylation and also induce several microRNAs including miR-155, miR-181b-1 and miR-146a. Adult HPA axis activity is regulated by (i) genetic factors, such as glucocorticoid receptor polymorphisms; (ii) epigenetic factors affecting glucocorticoid receptor function or expression, including the methylation status of alternative promoter regions of NR3C1 and the methylation of FKBP5 and HSD11β2 ; (iii) chronic inflammation and chronic nitrosative and oxidative stress. Finally, it is shown how severe psychological stress adversely affects mitochondrial structure and functioning and is associated with changes in brain mitochondrial DNA copy number and transcription; mitochondria can act as couriers of childhood stress into adulthood.

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Genetic and epigenetic factors in the regulation of the immune response

Cited by 7 publications

References 76 publications

Monogenic Adult-Onset Inborn Errors of Immunity

Monogenic Adult-Onset Inborn Errors of Immunity

Understanding seasonal weight loss tolerance in dairy goats: a transcriptomics approach

Socioeconomic Deprivation, Adverse Childhood Experiences and Medical Disorders in Adulthood: Mechanisms and Associations

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