Loss of Interleukin-6 Influences Transcriptional Immune Signatures and Alters Bacterial Colonization in the Skin

The skin functions as a protective barrier to inhibit the entry of foreign pathogens, all the while hosting a diverse milieu of microorganisms. Over time, skin cells, immune cells, cytokines, and microbes interact to integrate the processes of maintaining the skin’s physical and immune barrier. In the present study, the basal expression of two immunologically divergent mouse strains C57BL/6 and BALB/c, as well as a strain on the C57 background lacking IL-6, was characterized. Additionally, cutaneous antimicrobial gene expression profiles and skin bacterial microbiome were assessed between strains. Total RNA sequencing was performed on untreated C57BL/6 (control), BALB/c, and IL-6-deficient skin samples and found over 3,400 genes differentially modulated between strains. It was found that each strain modulated its own transcriptional “profile” associated with skin homeostasis and also influenced the overall bacterial colonization as indicated by the differential phyla present on each strain. Together, these data not only provide a comprehensive view of the transcriptional changes in homeostatic skin of different mouse strains but also highlight the possible influence of the strain differences (e.g., Th1/Th2 balance) as well as a role for IL-6 in overall skin immunity and resident microbial populations.

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Keratin gene expression profiles after digit amputation in C57BL/6 vs. regenerative MRL mice imply an early regenerative keratinocyte activated-like state

Physiological Genomics ◽

10.1152/physiolgenomics.00142.2012 ◽

2013 ◽

Vol 45 (11) ◽

pp. 409-421 ◽

Cited By ~ 13

Author(s):

Chia-Ho Cheng ◽

John Leferovich ◽

Xiang-Ming Zhang ◽

Khamilia Bedelbaeva ◽

Dmitri Gourevitch ◽

...

Keyword(s):

Expression Profiles ◽

Gene Expression Profiles ◽

Strain Differences ◽

Mouse Strains ◽

Keratin Gene ◽

Expression Levels ◽

Tissue Sections ◽

Activated State ◽

Microarray Expression ◽

Microarray Analyses

Mouse strains C57BL/6 (B6) and MRL were studied by whole mouse genome chip microarray analyses of RNA isolated from amputation sites at different times pre- and postamputation at the midsecond phalange of the middle digit. Many keratin genes were highly differentially expressed. All keratin genes were placed into three temporal response classes determined by injury/preinjury ratios. One class, containing only Krt6 and Krt16, were uniquely expressed relative to the other two classes and exhibited different temporal responses in MRL vs. B6. Immunohistochemical staining for Krt6 and Krt16 in tissue sections, including normal digit, flank skin, and small intestine, and from normal and injured ear pinna tissue exhibited staining differences in B6 (low) and MRL (high) that were consistent with the microarray results. Krt10 staining showed no injury-induced differences, consistent with microarray expression. We analyzed Krt6 and Krt16 gene association networks and observed in uninjured tissue several genes with higher expression levels in MRL, but not B6, that were associated with the keratinocyte activated state: Krt6, Krt16, S100a8, S100a9, and Il1b; these data suggest that keratinocytes in the MRL strain, but not in B6, are in an activated state prior to wounding. These expression levels decreased in MRL at all times postwounding but rose in the B6, peaking at day 3. Other keratins significantly expressed in the normal basal keratinocyte state showed no significant strain differences. These data suggest that normal MRL skin is in a keratinocyte activated state, which may provide it with superior responses to wounding.

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Phenotypic and clonal stability of antigen-inexperienced memory-like T cells across the genetic background, hygienic status, and aging

10.1101/2020.09.01.277004 ◽

2020 ◽

Author(s):

Alena Moudra ◽

Veronika Niederlova ◽

Jiri Novotny ◽

Lucie Schmiedova ◽

Jan Kubovciak ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Genetic Background ◽

Expression Profiles ◽

Bacterial Colonization ◽

Gene Expression Profiles ◽

Inbred Strains ◽

Microbial Colonization ◽

Independent Manner ◽

Different Genetic Background

AbstractAntigen-inexperienced memory-like T (AIMT) cells are functionally unique T cells representing one of the two largest subsets of murine CD8+ T cells. However, differences between laboratory inbred strains, insufficient data from germ-free mice, a complete lack of data from feral mice, and unclear relationship between AIMT cells formation during aging represent major barriers for better understanding of their biology. We performed a thorough characterization of AIMT cells from mice of different genetic background, age, and hygienic status by flow cytometry and multi-omics approaches including analyses of gene expression, TCR repertoire, and microbial colonization. Our data showed that AIMT cells are steadily present in mice independently of their genetic background and hygienic status. Despite differences in their gene expression profiles, young and aged AIMT cells originate from identical clones. We identified that CD122 discriminates two major subsets of AIMT cells in a strain-independent manner. Whereas thymic CD122LOW AIMT cells (innate memory) prevail only in young animals with high thymic IL-4 production, peripheral CD122HIGH AIMT cells (virtual memory) dominate in aged mice. Co-housing with feral mice changed the bacterial colonization of laboratory strains, but had only minimal effects on the CD8+ T-cell compartment including AIMT cells.

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Abstract 268: Strain-specific Cardiac Fibroblast Response to Isoproterenol-induced Cardiac Fibrosis

Circulation Research ◽

10.1161/res.121.suppl_1.268 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Shuin Park ◽

Sara Ranjbarvaziri ◽

Fides Lay ◽

Peng Zhao ◽

Aldons J Lusis ◽

...

Keyword(s):

Gene Expression ◽

Cardiac Fibrosis ◽

Cardiac Fibroblasts ◽

Expression Profiles ◽

Inbred Mouse ◽

Gene Expression Profiles ◽

Mouse Strains ◽

Sequencing Analysis ◽

Different Strains

Fibroblasts are a heterogeneous population of cells that function within the injury response mechanisms across various tissues. Despite their importance in pathophysiology, the effects of different genetic backgrounds on fibroblast contribution to the development of disease has yet to be addressed. It has previously been shown that mice in the Hybrid Mouse Diversity Panel, which consists of 110 inbred mouse strains, display a spectrum in severity of cardiac fibrosis in response to chronic treatment of isoproterenol (ISO). Here, we characterized cardiac fibroblasts (CFbs) from three different mouse strains (C57BL/6J, C3H/HeJ, and KK/HIJ) which exhibited varying degrees of fibrosis after ISO treatment. The select strains of mice underwent sham or ISO treatment via intraperitoneally-implanted osmotic pumps for 21 days. Masson’s Trichrome staining showed significant differences in fibrosis in response to ISO, with KK/HIJ mice demonstrating the highest levels, C3H/HeJ exhibiting milder levels, and C57BL/6J demonstrating little to no fibrosis. When CFbs were isolated and cultured from each strain, the cells demonstrated similar traits at the basal level but responded to ISO stimuli in a strain-specific manner. Likewise, CFbs demonstrated differential behavior and gene expression in vivo in response to ISO. ISO treatment caused CFbs to proliferate similarly across all strains, however, immunofluorescence staining showed differential levels of CFb activation. Additionally, RNA-sequencing analysis revealed unique gene expression profiles of all three strains upon ISO treatment. Our study depicts the phenotypic heterogeneity of CFbs across different strains of mice and our results suggest that ISO-induced cardiac fibrosis is a complex process that is independent of fibroblast proliferation and is mainly driven by the activation/inhibition of genes involved in pro-fibrotic pathways.

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Gene Expression Profiles In Inbred Mouse Strains Following RSV Infection

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a4134 ◽

2010 ◽

Author(s):

Monica High ◽

Jennifer Fostel ◽

Fernando Polack ◽

Hye-Youn Cho ◽

Steven R. Kleeberger

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Inbred Mouse ◽

Gene Expression Profiles ◽

Mouse Strains ◽

Inbred Mouse Strains ◽

Rsv Infection

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Comparison of Host Gene Expression Profiles in Spleen Tissues of Genetically Susceptible and Resistant Mice during ECTV Infection

BioMed Research International ◽

10.1155/2017/6456180 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 5

Author(s):

Wen-Yu Cheng ◽

Huai-Jie Jia ◽

Xiao-Bing He ◽

Guo-Hua Chen ◽

Yuan Feng ◽

...

Keyword(s):

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Mapk Signaling ◽

Mouse Strains ◽

Resistant Mouse ◽

Gene Profiles ◽

Expression Of Genes ◽

Leukocyte Transendothelial Migration ◽

Specific Virus

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating the host-Orthopoxvirusrelationship as it relates to pathogenesis and the immune response. ECTV is a mouse-specific virus and causes high mortality in susceptible mice strains, including BALB/c and C3H, whereas C57BL/6 and 129 strains are resistant to the disease. To understand the host genetic factors in different mouse strains during the ECTV infection, we carried out a microarray analysis of spleen tissues derived from BALB/c and C57BL/6 mice, respectively, at 3 and 10 days after ECTV infection. Differential Expression of Genes (DEGs) analyses revealed distinct differences in the gene profiles of susceptible and resistant mice. The susceptible BALB/c mice generated more DEGs than the resistant C57BL/6 mice. Additionally, gene ontology and KEGG pathway analysis showed the DEGs of susceptible mice were involved in innate immunity, apoptosis, metabolism, and cancer-related pathways, while the DEGs of resistant mice were largely involved in MAPK signaling and leukocyte transendothelial migration. Furthermore, the BALB/c mice showed a strong induction of interferon-induced genes, which, however, were weaker in the C57BL/6 mice. Collectively, the differential transcriptome profiles of susceptible and resistant mouse strains with ECTV infection will be crucial for further uncovering the molecular mechanisms of the host-Orthopoxvirusinteraction.

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Genetic Predisposition to Hepatocarcinogenesis in Inbred and Outbred Mouse Lines Selected for High or Low Inflammatory Response

Journal of Immunology Research ◽

10.1155/2019/5298792 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Lilian Rego de Carvalho ◽

Andrea Borrego ◽

José Ricardo Jensen ◽

Wafa Hanna Koury Cabrera ◽

Aline Marques Santos ◽

...

Keyword(s):

Linkage Analysis ◽

Liver Tumors ◽

Expression Profiles ◽

Inbred Mice ◽

Tumor Development ◽

Gene Expression Profiles ◽

Differential Susceptibility ◽

Snp Markers ◽

Mouse Strains ◽

Specific Gene

AIRmax and AIRmin mouse strains phenotypically selected for high and low acute inflammatory responsiveness (AIR) are, respectively, susceptible or resistant to developing hepatocellular carcinoma (HCC) induced by the chemical carcinogens urethane and diethylnitrosamine (DEN). Early production of TNF-α, IL-1β, and IL-6 in the liver after DEN treatment correlated with tumor development in AIRmax mice. Transcriptome analysis of livers from untreated AIRmax and AIRmin mice showed specific gene expression profiles in each line, which might play a role in their differential susceptibility to HCC. Linkage analysis with SNP markers in F2 (AIRmax×AIRmin) intercross mice revealed two quantitative trait loci (QTL) in chromosomes 2 and 9, which are significantly associated with the number and progression of urethane-induced liver tumors. An independent linkage analysis with an intercross population from A/J and C57BL/6J inbred mice mapped regions in chromosomes 1 and 7 associated with the progression of urethane-induced liver tumors, evidencing the heterogeneity of HCC genetic control.

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Genes of the GadX-GadW Regulon in Escherichia coli

Journal of Bacteriology ◽

10.1128/jb.185.10.3190-3201.2003 ◽

2003 ◽

Vol 185 (10) ◽

pp. 3190-3201 ◽

Cited By ~ 86

Author(s):

Don L. Tucker ◽

Nancy Tucker ◽

Zhuo Ma ◽

John W. Foster ◽

Regina L. Miranda ◽

...

Keyword(s):

Escherichia Coli ◽

Target Genes ◽

Expression Profiles ◽

Bacterial Colonization ◽

Gene Expression Profiles ◽

Acid Resistance ◽

Principal Component ◽

Growth Conditions ◽

Negative Control ◽

Wild Type

ABSTRACT Acid in the stomach is thought to be a barrier to bacterial colonization of the intestine. Escherichia coli, however, has three systems for acid resistance, which overcome this barrier. The most effective of these systems is dependent on transport and decarboxylation of glutamate. GadX regulates two genes that encode isoforms of glutamate decarboxylase critical to this system, but additional genes associated with the glutamate-dependent acid resistance system remained to be identified. The gadX gene and a second downstream araC-like transcription factor gene, gadW, were mutated separately and in combination, and the gene expression profiles of the mutants were compared to those of the wild-type strain grown in neutral and acidified media under conditions favoring induction of glutamate-dependent acid resistance. Cluster and principal-component analyses identified 15 GadX-regulated, acid-inducible genes. Reverse transcriptase mapping demonstrated that these genes are organized in 10 operons. Analysis of the strain lacking GadX but possessing GadW confirmed that GadX is a transcriptional activator under acidic growth conditions. Analysis of the strain lacking GadW but possessing GadX indicated that GadW exerts negative control over three GadX target genes. The strain lacking both GadX and GadW was defective in acid induction of most but not all GadX target genes, consistent with the roles of GadW as an inhibitor of GadX-dependent activation of some genes and an activator of other genes. Resistance to acid was decreased under certain conditions in a gadX mutant and even more so by combined mutation of gadX and gadW. However, there was no defect in colonization of the streptomycin-treated mouse model by the gadX mutant in competition with the wild type, and the gadX gadW mutant was a better colonizer than the wild type. Thus, E. coli colonization of the mouse does not appear to require glutamate-dependent acid resistance.

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Differential basal expression of immune genes confers Crassostrea gigas resistance to Pacific Oyster Mortality Syndrome

10.21203/rs.2.16448/v2 ◽

2020 ◽

Author(s):

de Lorgeril Julien ◽

Bruno Petton ◽

Aude Lucasson ◽

Valérie Perez ◽

Pierre-Louis Stenger ◽

...

Keyword(s):

Stress Responses ◽

Pacific Oyster ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Dna Integrity ◽

Immune Genes ◽

Basal Expression ◽

Oyster Mortality ◽

Underlying Mechanisms ◽

Polymicrobial Disease

Abstract Background: As a major threat to the oyster industry, Pacific Oyster Mortality Syndrome (POMS) is a polymicrobial disease affecting the main oyster species farmed across the world. POMS affects oyster juveniles and became panzootic this last decade, but POMS resistance in some oyster genotypes has emerged. While we know some genetic loci associated with resistance, the underlying mechanisms remained uncharacterized. So, we developed a comparative transcriptomic approach using basal gene expression profiles between different oyster biparental families with contrasted phenotypes when confronted to POMS (resistant or susceptible). Results: We showed that POMS resistant oysters show differential expression of genes involved in stress responses, protein modifications, maintenance of DNA integrity and repair, and immune and antiviral pathways. We found similarities and clear differences among different molecular pathways in the different resistant families. These results suggest that the resistance process is polygenic and partially varies according to the oyster genotype. Conclusions: We found differences in basal expression levels of genes related to TLR-NFκB, JAK-STAT and STING-RLR pathways. These differences could explain the best antiviral response, as well as the robustness of resistant oysters when confronted to POMS. As some of these genes represent valuable candidates for selective breeding, we propose future studies should further examine their function.

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Single-Cell transcriptional changes in hypothalamic CRH-expressing neurons after early-life adversity inform enduring alterations in responses to stress

10.1101/2021.08.31.458231 ◽

2021 ◽

Author(s):

Annabel K Short ◽

Christina Wilcox ◽

Yuncai Chen ◽

Aidan L Pham ◽

Matthew T Birnie ◽

...

Keyword(s):

Gene Expression ◽

Single Cell ◽

Stress Responses ◽

Life Stress ◽

Early Life ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Early Life Adversity ◽

Neuronal Populations ◽

Transcriptional Changes

AbstractMental and cognitive health, as well as vulnerability to neuropsychiatric disorders, involve the interplay of genes with the environment, particularly during sensitive developmental periods. Early-life stress / adversity (ELA) promotes vulnerabilities to stress-related affective disorders, yet it is unknown how a transient ELA dictates life-long neuroendocrine and behavioral reactions to stress. The population of hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons that regulate stress-responses is a promising candidate to mediate the enduring influences of ELA on stress-related behavioral and hormonal responses via enduring transcriptional and epigenetic mechanisms. Capitalizing on a well-characterized model of ELA, we examined here the ELA-induced changes in gene expression profiles of stress-sensitive CRH-neurons in the hypothalamic paraventricular nucleus (PVN) of male mice. Given the known heterogeneity of these neuronal populations, we employed single-cell RNA sequencing (RNA-seq) approaches. The use of single-cell transcriptomics identified distinct CRH-expressing neuronal populations characterized by both their gene expression repertoire and their neurotransmitter profiles. Expression changes provoked by ELA clustered around genes involved in neuronal differentiation, synapse formation, altered energy metabolism and the cellular responses to stress and injury. Notably, the ELA-induced transcriptional changes took place primarily in subpopulations of glutamatergic CRH cells. Finally, ELA-induced transcriptional reprogramming of hypothalamic CRH-expressing neurons heralded significant, enduring disruptions of both hormonal and behavioral responses to stress throughout life.

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