Vanja lazarevic

INTRODUCTION: Interferon-gamma (IFN-γ) is pivotal in orchestrating immune responses during healthy pregnancy. However, its dysregulation, often due to autoimmunity, infections, or chronic inflammatory conditions, is implicated in adverse reproductive outcomes such as pregnancy failure or infertility. Additionally, the underlying immunological mechanisms remain elusive. METHODS: Here, we explore the impact of systemic IFN-γ elevation on cytotoxic T cell responses in female reproduction utilizing a systemic lupus-prone mouse model with impaired IFN-γ degradation...

Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted...

T-bet-expressing Th17 (T-bet+ RORγt+ ) cells are associated with the induction of pathology during experimental autoimmune encephalomyelitis (EAE) and the encephalitic nature of these Th17 cells can be explained by their ability to produce GM-CSF. However, the upstream regulatory mechanisms that control Csf2 (gene encoding GM-CSF) expression are still unclear. In this study, we found that Th17 cells dynamically expressed GATA3, the master transcription factor for Th2 cell differentiation, during their differentiation both in vitro and in vivo ...

CD4+ T helper 17 (TH 17) cells protect barrier tissues but also trigger autoimmunity. The mechanisms behind these opposing processes remain unclear. Here, we found that the transcription factor EGR2 controlled the transcriptional program of pathogenic TH 17 cells in the central nervous system (CNS) but not that of protective TH 17 cells at barrier sites. EGR2 was significantly elevated in myelin-reactive CD4+ T cells from patients with multiple sclerosis and mice with autoimmune neuroinflammation. The EGR2 transcriptional program was intricately woven within the TH 17 cell transcriptional regulatory network and showed high interconnectivity with core TH 17 cell-specific transcription factors...

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Corporal punishment (CP) is a widely spread disciplining practice among parents and caregivers globally. Our paper aimed to explore the relationship between the parental attitudes towards CP, expected outcomes of CP, and parenting practices on one hand, with the reported dysfunctions of their children, on the other. Additionally, we aimed to explore the relationship between the use of CP and the reported academic, developmental, and psychological-emotional dysfunctions of their children. The present study involved a nationally representative sample of 1186 parents in Serbia, who had at least one child aged 0-18 years at the moment of interviewing...

Prevention programs are a key method to reduce the prevalence and impact of mental health disorders in childhood and adolescence. Caregiver participation engagement (CPE), which includes caregiver participation in sessions as well as follow-through with homework plans, is theorized to be an important component in the effectiveness of these programs. This systematic review aims to (1) describe the terms used to operationalize CPE and the measurement of CPE in prevention programs, (2) identify factors associated with CPE, (3) examine associations between CPE and outcomes, and (4) explore the effects of strategies used to enhance CPE...

Signal tranducer and activator of transcription 5 (STAT5) plays a critical role in mediating cellular responses following cytokine stimulation. STAT proteins critically signal via the formation of dimers, but additionally, STAT tetramers serve key biological roles, and we previously reported their importance in T and natural killer (NK) cell biology. However, the role of STAT5 tetramerization in autoimmune-mediated neuroinflammation has not been investigated. Using the STAT5 tetramer-deficient Stat5a - Stat5b N-domain double knockin (DKI) mouse strain, we report here that STAT5 tetramers promote the pathogenesis of experimental autoimmune encephalomyelitis (EAE)...

Integrin CD103 mediates the adhesion and tissue retention of T cells by binding to E-cadherin which is abundant on epithelial cells. Notably, CD103 is highly expressed on CD8 T cells but conspicuously absent on most CD4 T cells. The mechanism controlling such lineage-specific expression of CD103 remains unclear. Using a series of genetically engineered mouse models, here, we demonstrate that the regulatory mechanism of CD103 expression is distinct between CD4 and CD8 T cells, and that the transcription factor Runx3 plays an important but not an essential role in this process...

MicroRNA miR-155 is an important regulatory molecule in the immune system and is highly expressed and functional in Th17 cells, a subset of CD4+ T helper cells which are key players in autoimmune diseases. Small molecules that can modulate miR-155 may potentially provide new therapeutic avenues to inhibit Th17 cell-mediated autoimmune diseases. Here, we present a novel high-throughput screening assay using primary T cells from genetically engineered Mir155 reporter mice, and its use to screen libraries of small molecules to identify novel modulators of Th17 cell function...

Once alerted to the presence of a pathogen, activated CD4+ T cells initiate distinct gene expression programs that produce multiple functionally specialized T helper (Th) subsets. The cytokine milieu present at the time of antigen encounter instructs CD4+ T cells to differentiate into interferon-(IFN)-γ-producing Th1 cells, interleukin-(IL)-4-producing Th2 cells, IL-17-producing Th17 cells, follicular T helper (Tfh) cells, or regulatory T (Treg) cells. In each of these Th cell subsets, a single transcription factor has been identified as a critical regulator of its specialized differentiation program...

OBJECTIVES: This study examined family dynamics as a moderator of the association between discrimination and both depression and life satisfaction for Latino youth. Specifically, we hypothesized that discrimination would have a negative impact on depression and life satisfaction. We also hypothesized that negative family dynamics would compound the negative impact of discrimination, whereas positive family dynamics would buffer against the impact of discrimination on depression and life satisfaction...

Th17 cells are critical drivers of autoimmune diseases and immunopathology. There is an unmet need to develop therapies targeting pathogenic Th17 cells for the treatment of autoimmune disorders. Here, we report that anxiolytic FGIN-1-27 inhibits differentiation and pathogenicity of Th17 cells in vitro and in vivo using the experimental autoimmune encephalomyelitis (EAE) model of Th17 cell-driven pathology. Remarkably, we found that the effects of FGIN-1-27 were independent of translocator protein (TSPO), the reported target for this small molecule, and instead were driven by a metabolic switch in Th17 cells that led to the induction of the amino acid starvation response and altered cellular fatty acid composition...

Using a bioecological perspective, the current study explored the dynamic relationship between a proximal process (i.e., language brokering [LB]), LB perceptions, environmental stress context, and timing of LB experiences on well-being. College students (N = 559; 19.6% Asian American, 32.0% European American, 33.5% Latino, and 14.9% multiracial/other ethnicity) reported on LB frequency, feelings about LB as a burden or source of role reversal, perceived stress, age of LB onset, and health (i.e., height, weight, somatic symptoms)...

The cross-talk between the microbiota and the immune system plays a fundamental role in the control of host physiology. However, the tissue-specific factors controlling this dialogue remain poorly understood. Here we demonstrate that T cell responses to commensal colonization are associated with the development of organized cellular clusters within the skin epithelium. These organized lymphocyte clusters are surrounded by keratinocytes expressing a discrete program associated with antigen presentation and antimicrobial defense...

The speed of impulse transmission is critical for optimal neural circuit function, but it is unclear how the appropriate conduction velocity is established in individual axons. The velocity of impulse transmission is influenced by the thickness of the myelin sheath and the morphology of electrogenic nodes of Ranvier along axons. Here we show that myelin thickness and nodal gap length are reversibly altered by astrocytes, glial cells that contact nodes of Ranvier. Thrombin-dependent proteolysis of a cell adhesion molecule that attaches myelin to the axon (neurofascin 155) is inhibited by vesicular release of thrombin protease inhibitors from perinodal astrocytes...

Periodontitis is one of the most common human inflammatory diseases, yet the mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion of resident memory T helper 17 (TH 17) cells in human periodontitis. Phenocopying humans, TH 17 cells expanded in murine experimental periodontitis through local proliferation. Unlike homeostatic oral TH 17 cells, which accumulate in a commensal-independent and interleukin-6 (IL-6)-dependent manner, periodontitis-associated expansion of TH 17 cells was dependent on the local dysbiotic microbiome and required both IL-6 and IL-23...

Acquired and genetic immunodeficiencies have revealed an indispensable role for CD4+ T cells in the induction of protective host immune responses against a myriad of microbial pathogens. Influenced by the cytokines present in the microenvironment, activated CD4+ T cells may differentiate into several highly-specialized helper subsets defined by the production of distinct signature cytokines tailored to combat diverse classes of pathogens. The process of specification and differentiation is controlled by networks of core, master, and accessory transcription factors, which ensure that CD4+ T helper (TH ) cell responses mounted against an invading microbe are of the correct specificity and type...

In the version of this article initially published, in second paragraph of the second subsection of Results ('Peripheral licensing of CD4+ TH 17 cells in Tbx21-/- hosts'), the figure citation ('Fig. 1c') in the sentence that begins "In addition to" was incorrect. The correct citation is 'Fig. 1d'.

AIMS: The present study was designed to compare the ameliorating potential of pre- and post-treatments with melatonin, a potent natural antioxidant, in the carbon tetrachloride-induced rat liver damage model by tracking changes in enzymatic and non-enzymatic liver tissue defense parameters, as well as in the occurring pathohistological changes. MAIN METHODS: Rats from two experimental groups were treated with melatonin before and after CCl4 administration, while the controls, negative and positive, received vehicle/melatonin and CCl4 , respectively...