scholarly journals Autophagy-Associated IL-15 Production Is Involved in the Pathogenesis of Leprosy Type 1 Reaction

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2215
Author(s):  
Bruno Jorge de Andrade Silva ◽  
Tamiris Lameira Bittencourt ◽  
Thyago Leal-Calvo ◽  
Mayara Abud Mendes ◽  
Rhana Berto da Silva Prata ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Skin Cells ◽  
Expression Of Genes ◽  
Autophagy Induction ◽  
Autophagy Pathway ◽  
Ifn Γ ◽  
And Function

Leprosy reactional episodes are acute inflammatory events that may occur during the clinical course of the disease. Type 1 reaction (T1R) is associated with an increase in neural damage, and the understanding of the molecular pathways related to T1R onset is pivotal for the development of strategies that may effectively control the reaction. Interferon-gamma (IFN-γ) is a key cytokine associated with T1R onset and is also associated with autophagy induction. Here, we evaluated the modulation of the autophagy pathway in Mycobacterium leprae-stimulated cells in the presence or absence of IFN-γ. We observed that IFN-γ treatment promoted autophagy activation and increased the expression of genes related to the formation of phagosomes, autophagy regulation and function, or lysosomal pathways in M. leprae-stimulated cells. IFN-γ increased interleukin (IL)-15 secretion in M. leprae-stimulated THP-1 cells in a process associated with autophagy activation. We also observed higher IL15 gene expression in multibacillary (MB) patients who later developed T1R during clinical follow-up when compared to MB patients who did not develop the episode. By overlapping gene expression patterns, we observed 13 common elements shared between T1R skin lesion cells and THP-1 cells stimulated with both M. leprae and IFN-γ. Among these genes, the autophagy regulator Translocated Promoter Region, Nuclear Basket Protein (TPR) was significantly increased in T1R cells when compared with non-reactional MB cells. Overall, our results indicate that IFN-γ may induce a TPR-mediated autophagy transcriptional program in M. leprae-stimulated cells similar to that observed in skin cells during T1R by a pathway that involves IL-15 production, suggesting the involvement of this cytokine in the pathogenesis of T1R.

scholarly journals Remnants of ancestral larval eyes in an eyeless mollusk? Molecular characterization of photoreceptors in the scaphopod Antalis entalis

EvoDevo ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Tim Wollesen ◽  
Carmel McDougall ◽  
Detlev Arendt
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Binding Domain ◽  
Animal Evolution ◽  
Protein Activation ◽  
Expression Of Genes ◽  
Similar Gene Expression Profile ◽  
And Function

Abstract Background Eyes have evolved and been lost multiple times during animal evolution, however, the process of eye loss has only been reconstructed in a few cases. Mollusks exhibit eyes as varied as the octopod camera eye or the gastropod cup eye and are ideal systems for studying the evolution of eyes, photoreceptors, and opsins. Results Here, we identify genes related to photoreceptor formation and function in an eyeless conchiferan mollusk, the scaphopod Antalis entalis, and investigate their spatial and temporal expression patterns during development. Our study reveals that the scaphopod early mid-stage trochophore larva has putative photoreceptors in a similar location and with a similar gene expression profile as the trochophore of polyplacophoran mollusks. The apical and post-trochal putative photoreceptors appear to co-express go-opsin, six1/2, myoV, and eya, while expression domains in the posterior foot and pavilion (posterior mantle opening) show co-expression of several other candidate genes but not go-opsin. Sequence analysis reveals that the scaphopod Go-opsin amino acid sequence lacks the functionally important lysine (K296; Schiff base) in the retinal-binding domain, but has not accumulated nonsense mutations and still exhibits the canonical G-protein activation domain. Conclusions The scaphopod Go-opsin sequence reported here is the only known example of a bilaterian opsin that lacks lysine K296 in the retinal-binding domain. Although this may render the Go-opsin unable to detect light, the protein may still perform sensory functions. The location, innervation, development, and gene expression profiles of the scaphopod and polyplacophoran apical and post-trochal photoreceptors suggest that they are homologous, even though the scaphopod post-trochal photoreceptors have degenerated. This indicates that post-trochal eyes are not a polyplacophoran apomorphy but likely a molluscan synapomorphy lost in other mollusks. Scaphopod eye degeneration is probably a result of the transition to an infaunal life history and is reflected in the likely functional degeneration of Go-opsin, the loss of photoreceptor shielding pigments, and the scarce expression of genes involved in phototransduction and eye development. Our results emphasize the importance of studying a phylogenetically broad range of taxa to infer the mechanisms and direction of body plan evolution.

Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 2090-2093 ◽  
Author(s):  
Dirk Kienle ◽  
Axel Benner ◽  
Alexander Kröber ◽  
Dirk Winkler ◽  
Daniel Mertens ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Expression Of Genes ◽  
Vh Genes ◽  
Signaling Activation

The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in chronic lymphocytic leukemia (CLL). To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor (BCR) signaling/activation, cell cycle, and apoptosis control in CLL using these specific VH genes compared to VH mutated (VH-MUT) and VH unmutated (VH-UM) CLL not using these VH genes. V3-21 cases showed characteristic expression differences compared to VH-MUT (up: ZAP70 [or ZAP-70]; down: CCND2, P27) and VH-UM (down: PI3K, CCND2, P27, CDK4, BAX) involving several BCR-related genes. Similarly, there was a marked difference between VH unmutated cases using the V1-69 gene and VH-UM (up: FOS; down: BLNK, SYK, CDK4, TP53). Therefore, usage of specific VH genes appears to have a strong influence on the gene expression pattern pointing to antigen recognition and ongoing BCR stimulation as a pathogenic factor in these CLL subgroups.

scholarly journals BHLHE40 Regulates IL-10 and IFN-γ Production in T Cells but Does Not Interfere With Human Type 1 Regulatory T Cell Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Molly Javier Uyeda ◽  
Robert A. Freeborn ◽  
Brandon Cieniewicz ◽  
Rosa Romano ◽  
Ping (Pauline) Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Ex Vivo ◽  
Surface Expression ◽  
Surface Molecules ◽  
Ifn Γ ◽  
And Function ◽  
Tr1 Cells

Type 1 regulatory T (Tr1) cells are subset of peripherally induced antigen-specific regulatory T cells. IL-10 signaling has been shown to be indispensable for polarization and function of Tr1 cells. However, the transcriptional machinery underlying human Tr1 cell differentiation and function is not yet elucidated. To this end, we performed RNA sequencing on ex vivo human CD49b+LAG3+ Tr1 cells. We identified the transcription factor, BHLHE40, to be highly expressed in Tr1 cells. Even though Tr1 cells characteristically produce high levels of IL-10, we found that BHLHE40 represses IL-10 and increases IFN-γ secretion in naïve CD4+ T cells. Through CRISPR/Cas9-mediated knockout, we determined that IL10 significantly increased in the sgBHLHE40-edited cells and BHLHE40 is dispensable for naïve CD4+ T cells to differentiate into Tr1 cells in vitro. Interestingly, BHLHE40 overexpression induces the surface expression of CD49b and LAG3, co-expressed surface molecules attributed to Tr1 cells, but promotes IFN-γ production. Our findings uncover a novel mechanism whereby BHLHE40 acts as a regulator of IL-10 and IFN-γ in human CD4+ T cells.

scholarly journals Early Response of CD8+ T Cells in COVID-19 Patients

2021 ◽  
Vol 11 (12) ◽  
pp. 1291
Author(s):  
Deni Ramljak ◽  
Martina Vukoja ◽  
Marina Curlin ◽  
Katarina Vukojevic ◽  
Maja Barbaric ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Mrna Expression ◽  
Cd8 T Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Effector Memory ◽  
Healthy Controls ◽  
Ifn Γ

Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.

scholarly journals Three Years Follow-Up Study Showed Prenatal Methamphetamine Exposure May Cause Chronic Abnormalities In Transcriptomic Pattern

2021 ◽  
Author(s):  
Arvin Haghighatfard ◽  
Soha Seifollahi ◽  
Pegah Rajabi ◽  
Niloofar Rahmani ◽  
Rojin Ghannadzadeh
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Childbearing Age ◽  
Methamphetamine Use ◽  
Methamphetamine Use Disorder

Abstract Background: The high rate of methamphetamine use disorder among young adults and women of childbearing age makes it imperative to clarify the long-term effects of Methamphetamine exposure on the offspring. Behavioral and cognitive problems had been reported in children with parental Methamphetamine exposure (PME). The present study aimed to assess the acute and chronic effects of PME in molecular regulations and gene expression profiles of children during their first years of life.Methods: All subjects were recruited before birth, and sampling was conducted from the first ten days of birth, twelve months, twenty months, and thirty-six months of age. Finally, 2658 children with PME and 3573 normal children had been finished the follow-up. RNA extraction was operated from blood samples and gene expression profiling was conducted by using the Affymetrix GeneChip Human Genome U133 plus 2.0 Array Platform. Gene expression data were confirmed by Real-time PCR. Results: Gene expression profiling during thirty-six months showed several constant mRNA level alterations in children with PME compared with normal. These genes are involved in several gene ontologies and pathways involved with the immune system, neuronal functions, and bioenergetic metabolism. It seems that Methamphetamine use disorder before and during the pregnancy period may affect the expression profile of children, and these changes could remain years after birth. Affected genes have some similarities with the gene expression patterns of addiction, psychiatric disorders, neurodevelopmental disabilities, and immune deficiencies. Conclusion: Findings may shed light on the molecular effects of prenatal methamphetamine exposure and may lead to new psychological and somatic caring protocols for these children based on their potential abnormalities.

scholarly journals Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

2019 ◽  
Vol 117 (38) ◽  
pp. 23317-23322 ◽  
Author(s):  
Joaquín Sanz ◽  
Paul L. Maurizio ◽  
Noah Snyder-Mackler ◽  
Noah D. Simons ◽  
Tawni Voyles ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Status ◽  
Social History ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Expression Patterns ◽  
Social Experience ◽  
Type I ◽  
Gene Expression Response ◽  
Expression Of Genes

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB–dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB– and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history—in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

scholarly journals Infection with Human Immunodeficiency Virus Type 1 Upregulates DNA Methyltransferase, Resulting in De Novo Methylation of the Gamma Interferon (IFN-γ) Promoter and Subsequent Downregulation of IFN-γ Production

1998 ◽  
Vol 18 (9) ◽  
pp. 5166-5177 ◽  
Author(s):  
Judy A. Mikovits ◽  
Howard A. Young ◽  
Paula Vertino ◽  
Jean-Pierre J. Issa ◽  
Paula M. Pitha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Methylation Status ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Hiv 1 ◽  
De Novo Methylation

ABSTRACT The immune response to pathogens is regulated by a delicate balance of cytokines. The dysregulation of cytokine gene expression, including interleukin-12, tumor necrosis factor alpha, and gamma interferon (IFN-γ), following human retrovirus infection is well documented. One process by which such gene expression may be modulated is altered DNA methylation. In subsets of T-helper cells, the expression of IFN-γ, a cytokine important to the immune response to viral infection, is regulated in part by DNA methylation such that mRNA expression inversely correlates with the methylation status of the promoter. Of the many possible genes whose methylation status could be affected by viral infection, we examined the IFN-γ gene as a candidate. We show here that acute infection of cells with human immunodeficiency virus type 1 (HIV-1) results in (i) increased DNA methyltransferase expression and activity, (ii) an overall increase in methylation of DNA in infected cells, and (iii) the de novo methylation of a CpG dinucleotide in the IFN-γ gene promoter, resulting in the subsequent downregulation of expression of this cytokine. The introduction of an antisense methyltransferase construct into lymphoid cells resulted in markedly decreased methyltransferase expression, hypomethylation throughout the IFN-γ gene, and increased IFN-γ production, demonstrating a direct link between methyltransferase and IFN-γ gene expression. The ability of increased DNA methyltransferase activity to downregulate the expression of genes like the IFN-γ gene may be one of the mechanisms for dysfunction of T cells in HIV-1-infected individuals.

Gene expression analysis in burn wounds of rats

2002 ◽  
Vol 283 (4) ◽  
pp. R918-R930 ◽  
Author(s):  
Marcus Spies ◽  
Mohan R. K. Dasu ◽  
Nenad Svrakic ◽  
Olivera Nesic ◽  
Robert E. Barrow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Growth Regulation ◽  
Cell Metabolism ◽  
Expression Patterns ◽  
Burn Wound ◽  
Oligonucleotide Arrays ◽  
Burn Wound Healing ◽  
Expression Of Genes ◽  
Systemic Responses

The events occurring early in the burn wound trigger a sequence of local and systemic responses that influence cell and tissue survival and, consequently, wound healing and recovery. Using high-density oligonucleotide arrays we identified gene expression patterns in skin samples taken from a region of injury in the burn rat model. The associated genomic events include the differential expression of genes involved in cell survival and death, cell growth regulation, cell metabolism, inflammation, and immune response. The functional gene cluster detected and their time appearance matched the time sequence known to occur in burn wound healing.

scholarly journals Cannulated Cancellous Screw Fixation for Capitellum Fractures in Adolescents

2011 ◽  
Vol 19 (3) ◽  
pp. 346-349 ◽  
Author(s):  
Kee Leong Ong ◽  
Arjandas Mahadev
Keyword(s):  
Performance Index ◽  
Kirschner Wire ◽  
Excellent Outcome ◽  
Excellent Functional Outcome ◽  
Cancellous Screws ◽  
The Mean ◽  
And Function ◽  
Anterior Direction

Purpose. To review the outcome of 9 adolescents treated with 2 to 3 cannulated cancellous screws for type-1 capitellum fractures. Methods. Records of 8 boys and one girl aged 12 to 14 (mean, 14) years with type-1 capitellum fractures were reviewed. The mechanism of injury was a fall on the flexed elbow. No patient had associated injuries or neurovascular compromise. In 2 patients, the fracture was minimally displaced and treated with a cast. The remaining 7 patients with displaced fractures underwent open reduction and internal fixation using 4.0-mm cannulated partially threaded cancellous screws inserted in a posterior-to-anterior direction. In one patient, a Kirschner wire was added to fix a small comminuted fragment. Elbow pain, range of motion, stability, and function were evaluated using the Mayo Elbow Performance Index. Results. The mean follow-up period was 7 (range, 2–18) months. The mean Mayo Elbow Performance Index score was 100, indicating excellent outcome. No patient developed avascular necrosis or heterotrophic ossification. All patients achieved anatomic bone union. All implants were removed after a mean of 4.7 (range, 2–7) months. Conclusion. The fixation of type-1 capitellum fractures with 2 to 3 cannulated cancellous screws inserted posteroanteriorly achieved excellent functional outcome.

scholarly journals Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes That Govern Cardiomyocyte Maturation

2020 ◽  
Vol 178 (2) ◽  
pp. 325-337
Author(s):  
Matthew de Gannes ◽  
Chia-I Ko ◽  
Xiang Zhang ◽  
Jacek Biesiada ◽  
Liang Niu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Heart Development ◽  
Expression Patterns ◽  
Embryonic Stem Cell Line ◽  
Molecular Networks ◽  
Unknown Etiology ◽  
Postnatal Maturation ◽  
Complex Interactions ◽  
And Function

Abstract Congenital heart disease (CHD), the leading birth defect worldwide, has a largely unknown etiology, likely to result from complex interactions between genetic and environmental factors during heart development, at a time when the heart adapts to diverse physiological and pathophysiological conditions. Crucial among these is the regulation of cardiomyocyte development and postnatal maturation, governed by dynamic changes in DNA methylation. Previous work from our laboratory has shown that exposure to the environmental toxicant tetrachlorodibenzo-p-dioxin (TCDD) disrupts several molecular networks responsible for heart development and function. To test the hypothesis that the disruption caused by TCDD in the heart results from changes in DNA methylation and gene expression patterns of cardiomyocytes, we established a stable mouse embryonic stem cell line expressing a puromycin resistance selectable marker under control of the cardiomyocyte-specific Nkx2-5 promoter. Differentiation of these cells in the presence of puromycin induces the expression of a large suite of cardiomyocyte-specific markers. To assess the consequences of TCDD treatment on gene expression and DNA methylation in these cardiomyocytes, we subjected them to transcriptome and methylome analyses in the presence of TCDD. Unlike control cardiomyocytes maintained in vehicle, the TCDD-treated cardiomyocytes showed extensive gene expression changes, with a significant correlation between differential RNA expression and DNA methylation in 111 genes, many of which are key elements of pathways that regulate cardiovascular development and function. Our findings provide an important clue toward the elucidation of the complex interactions between genetic and epigenetic mechanisms after developmental TCDD exposure that may contribute to CHD.

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