Helios transcription factor and semaphorin receptor Nrp-1 were originally described as constitutively expressed at high levels on CD4+Foxp3+ T regulatory cells of intrathymic origin (tTregs). On the ...other hand, CD4+Foxp3+ Tregs generated in the periphery (pTregs) or induced ex vivo (iTregs) were reported to express low levels of Helios and Nrp-1. Soon afterwards the reliability of Nrp-1 and Helios as markers discriminating between tTregs and pTregs was questioned and until now no consensus has been reached. Here, we used several genetically modified mouse strains that favor pTregs or tTregs formation and analyzed the TCR repertoire of these cells. We found that Tregs with variable levels of Nrp-1 and Helios were abundant in mice with compromised ability to support natural differentiation of tTregs or pTregs. We also report that TCR repertoires of Treg clones expressing high or low levels of Nrp-1 or Helios are similar and more alike repertoire of CD4+Foxp3+ than repertoire of CD4+Foxp3- thymocytes. These results show that high vs. low expression of Nrp-1 or Helios does not unequivocally identify Treg clones of thymic or peripheral origin.
The human gut microbiota is a diverse and complex ecosystem that is involved in beneficial physiological functions as well as disease pathogenesis. Blastocystis is a common protistan parasite and is ...increasingly recognized as an important component of the gut microbiota. The correlations between Blastocystis and other communities of intestinal microbiota have been investigated, and, to a lesser extent, the role of this parasite in maintaining the host immunological homeostasis. Despite recent studies suggesting that Blastocystis decreases the abundance of beneficial bacteria, most reports indicate that Blastocystis is a common component of the healthy gut microbiome. This review covers recent finding on the potential interactions between Blastocystis and the gut microbiota communities and its roles in regulating host immune responses.
Misophonia is an underexplored condition that significantly decreases the quality of life of those who suffer from it. It has neurological and physiological correlates and is associated with a ...variety of psychiatric symptoms; however, a growing body of data suggests that it is a discrete disorder. While comorbid diagnoses among people with misophonia have been a matter of research interest for many years there is no data on the frequency of misophonia among people with psychiatric disorders. This could be the next step to reveal additional mechanisms underlying misophonia. Until recently, the use of a variety of non-validated questionnaires and the dominance of internet-based studies have been also a major obstacles to a proper definition of misophonia. A total of 94 inpatients diagnosed with depression were assessed for misophonia with face-to-face interviews as well as with MisoQuest-a validated misophonia questionnaire. The prevalence of misophonia among these patients and the congruence of MisoQuest with face-to-face interviews were evaluated. Additionally, the patients filled in a series of questionnaires that measured a variety of psychiatric symptoms and psychological traits. Anxiety, depression, impulsivity, somatic pain, vegetative symptoms, post-traumatic stress disorder (PTSD) symptoms, gender, and age were analyzed in relation to the severity of symptoms of misophonia. Between 8.5 to 12.76% of inpatients with depression were diagnosed with misophonia (depending on measurement and inclusion criteria). MisoQuest accuracy was equal to 92.55%, sensitivity-66.67% and specificity-96.34%. Severity of misophonia symptoms was positively correlated to the greatest extent with anxiety. Moderate positive correlation was also found between severity of misophonia symptoms and depressive symptoms, intrusions, and somatic pain; a weak positive correlation was found between severity of misophonia and non-planning impulsivity, motor impulsivity, avoidance, and vegetative symptoms. There was no relationship between the severity of misophonia symptoms and attentional impulsivity or the age of participants.
In the article, we review key methodological issues and study results on the heritability of political attitudes. These studies show to what degree the variance of observed attitudes can be explained ...by genetic variance. We have analysed studies differing in terms of applied methods, techniques and research tools, as well as sample populations of different age and sex structures. Regardless of these differences, the studies show that political attitudes are most likely influenced to some extent by genetic factors. This research suggests that the influence of genes on attitudes is subject to change over the life cycle. It also provides knowledge regarding the mechanisms that may link genes and attitudes. The studies conducted to date offer the opportunity to broaden the culturalism-based explanations of political attitudes with biological aspects; however, they also point to several issues that will require additional attention from the researchers.
Using the Regulative Theory of Temperament, this study aimed to identify relationships between two temperamental traits – activity and emotional reactivity – and functional connectivity of the ...amygdala and the anterior cingulate cortex during the Affective Stroop task. Participants were 84 young adults (42 women) aged 19–25. Emotional reactivity was negatively related to connectivity between the right amygdala and the left lateral occipital cortex, right cerebellum, and left inferior frontal gyrus (IFG) as well as right rostral anterior cingulate cortex (rACC)–frontal pole connectivity. Temperamental activity was related to right amygdala–left subcallosal cortex positive connectivity; and right amygdala–left IFG, and left middle temporal gyrus (MTG) negative connectivity and rACC–cerebellum negative connectivity. The interaction between the two traits was related to the connectivity between the amygdala and right cerebellum, left subcallosal cortex, and left MTG, as well as right rACC–right prefrontal pole connectivity. Our results are in line with previous literature, suggesting diminished cognitive resources among individuals with ineffective regulatory temperamental systems.
•Reactivity is related to connectivity between amygdala and lateral and frontal areas•Activity is related to negative coupling of rACC with cerebellum•Trait interaction is related to negative amygdala-cerebellum coupling•Lessen cognitive resources is a possible effect of ineffective temperamental regulation
The large intestine harbors microorganisms playing unique roles in host physiology. The beneficial or detrimental outcome of host‐microbiome coexistence depends largely on the balance between ...regulators and responder intestinal CD4+ T cells. We found that ulcerative colitis‐like changes in the large intestine after infection with the protist Blastocystis ST7 in a mouse model are associated with reduction of anti‐inflammatory Treg cells and simultaneous expansion of pro‐inflammatory Th17 responders. These alterations in CD4+ T cells depended on the tryptophan metabolite indole‐3‐acetaldehyde (I3AA) produced by this single‐cell eukaryote. I3AA reduced the Treg subset in vivo and iTreg development in vitro by modifying their sensing of TGFβ, concomitantly affecting recognition of self‐flora antigens by conventional CD4+ T cells. Parasite‐derived I3AA also induces over‐exuberant TCR signaling, manifested by increased CD69 expression and downregulation of co‐inhibitor PD‐1. We have thus identified a new mechanism dictating CD4+ fate decisions. The findings thus shine a new light on the ability of the protist microbiome and tryptophan metabolites, derived from them or other sources, to modulate the adaptive immune compartment, particularly in the context of gut inflammatory disorders.
Synopsis
The unicellular eukaryote Blastocystis is a component of intestinal microbiome. Here, Blastocystis‐derived indole‐3‐acetaldehyde (I3AA) is shown to enhance CD4+ T cell reactivity toward gut flora, thus contributing to the pro‐inflammatory response in gut tissue.
Blastocystis ST7 degrades tryptophan to I3AA via a pathway involving aspartate aminotransferase
Exposure to I3AA enhances T cell reactivity through TCR‐dependent mechanisms and inhibits T lymphocyte exhaustion by reducing PD‐1 expression
I3AA compromises peripheral selection and reduces survival of regulatory T cells by suppressing TGFβ signaling and CD103 expression.
I3AA hinders the activity of regulatory T cells by antagonizing the AhR signaling pathway
An intestinal protist Blastocystis ST7 produces indole‐3‐acetaldehyde that modulates the adaptive immune system response in the context of gut inflammation.
A global increase in the prevalence of metabolic syndromes and digestive tract disorders, like food allergy or inflammatory bowel disease (IBD), has become a severe problem in the modern world. ...Recent decades have brought a growing body of evidence that links the gut microbiome's complexity with host physiology. Hence, understanding the mechanistic aspects underlying the synergy between the host and its associated gut microbiome are among the most crucial questions. The functionally diversified adaptive immune system plays a central role in maintaining gut and systemic immune homeostasis. The character of the reciprocal interactions between immune components and host-dwelling microbes or microbial consortia determines the outcome of the organisms' coexistence within the holobiont structure. It has become apparent that metabolic by-products of the microbiome constitute crucial multimodal transmitters within the host-microbiome interactome and, as such, contribute to immune homeostasis by fine-tuning of the adaptive arm of immune system. In this review, we will present recent insights and discoveries regarding the broad landscape of microbiome-derived metabolites, highlighting the role of these small compounds in the context of the balance between pro- and anti-inflammatory mechanisms orchestrated by the host T cell compartment.
In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the ...small intestine are TCRαβCD8αα
cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα
IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα
IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα
IELs and CD4
T cells express identical αβTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8αα
IELs and CD4
derived T cell hybridomas suggesting that some of TCRαβCD8αα
clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4
IELs and Foxp3CD4
T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3
sufficient or Foxp3
deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRαβCD8αα
in small intestine expends in situ in response to changes in microbial flora.
Previous research has shown that polymorphisms in the
gene are related to some psychiatric conditions, including alcohol dependence. These relationships are moderated by the level of adverse ...childhood experiences that one has undergone. Maladaptive metacognition, associated with symptoms of psychiatric disorders and disturbed emotional self-regulation, is also a strong predictor of problematic alcohol use. Recent studies suggest that maladaptive metacognitions may be part of the developmental pathway from childhood abuse to drinking problems. This study attempted to identify relationships between
polymorphisms and metacognitions about the positive effects of alcohol use and problematic drinking in a group differing in levels of childhood trauma.
The sample studied was composed of 502 female participants aged 18-25 years (M=21.78; SD=1.84). Positive metacognitions about alcohol use were measured with the Positive Alcohol Metacognitions Scale (PAMS) and problematic drinking was gauged using the WHO Alcohol Use Disorders Identification Test. Levels of childhood adverse experiences were determined with the use of the Childhood Questionnaire. A total of 18 single-nucleotide polymorphisms (SNPs) in the
gene were genotyped.
We did not find any interaction between the gene and childhood trauma on problematic drinking or metacognitions. However we identified a strong main effect of two SNPs of the
gene - rs755658 and rs1334894 - on the PAMS subscale measuring positive metacognitive beliefs about emotional self-regulation. We also found nominally significant relations of several other SNPs with metacognitions and problematic drinking. Additionally, we showed that positive alcohol metacognitions mediate the relationship between problematic drinking and both rs755658 and rs1334894.
Our results may shed some light on the biological underpinnings of the developmental pathway leading to problematic drinking through maladaptive metacognitions.
: Misophonia is a condition related to experiencing psychophysiological sensations when exposed to specific sound triggers. In spite of progress in research on the subject, a fully validated ...questionnaire assessing misophonia has not been published yet. The goal of this study was to create and validate a new questionnaire to measure misophonia.
: MisoQuest is based on the diagnostic criteria proposed by Schröder et al. in 2013, with minor changes implemented by the authors of MisoQuest. A total of 705 participants took part in the study, completing the online questionnaires. Exploratory Factor Analysis (EFA) and analyses using the Item Response Theory (IRT) were performed. Internal consistency was evaluated with Cronbach's alpha.
: The reliability of the MisoQuest was excellent (α = 0.955). The stability at five weeks was strong. There was a significant difference in results between people classified as those with misophonia and those without misophonia.
: MisoQuest has good psychometric values and can be helpful in the identification of misophonia. A deeper analysis showed that certain triggers might be more specific for people with misophonia. Consideration of violent behavior in response to misophonic triggers as a symptom of misophonia was undermined.
PDF
