scholarly journals Survey of extracellular communication of systemic and organ-specific inflammatory responses through cell free messenger RNA profiling in mice

2021 ◽  
Author(s):  
Jiali Zhuang ◽  
Arkaitz Ibarra ◽  
Alexander Acosta ◽  
Amy P Karns ◽  
Jonathan Aballi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Immune Cells ◽  
Messenger Rna ◽  
Gene Expression Pattern ◽  
The Body ◽  
Large Set ◽  
Jak Inhibitor ◽  
Mrna Profiling ◽  
Organ Specific

Inflammatory and immune responses are essential and dynamic biological processes that protect the body against acute and chronic adverse stimuli. While conventional protein markers have been used to evaluate systemic inflammatory response, the immunological response to stimulation is complex and involves modulation of a large set of genes and interacting signaling pathways of innate and adaptive immune systems. Therefore, there is a need for a non-invasive tool that can comprehensively evaluate and monitor molecular dysregulations associated with inflammatory and immune responses. Here we utilized cell-free messenger RNA (cf-mRNA) RNA-Seq whole transcriptome profiling to assess lipopolysaccharide (LPS) induced and JAK inhibitor modulated inflammatory and immune responses in mouse plasma samples. Considering that, both organ-specific recruitment of immune cells and organ resident bespoke immune cells contributes to restoration of organ homeostasis, we also examined LPS-induced gene-expression dysregulation of multiple organs to shed light on organ crosstalk. Cf-mRNA profiling displayed a pattern of systemic immune responses elicited by LPS and dysregulation of associated pathways. Moreover, attenuation of several inflammatory pathways, including STAT and interferon pathways, were observed following the treatment of JAK inhibitor. Lastly, we identified the dysregulation of liver-specific transcripts in cf-mRNA which reflected changes in the gene-expression pattern in this biological compartment. Collectively, using a preclinical model, we demonstrated the potential of plasma cf-mRNA profiling for systemic and organ-specific characterization of drug-induced molecular alterations that are associated with inflammatory and immune responses.

scholarly journals An Extensive Genetic Program Occurring during Postnatal Growth in Multiple Tissues

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1791-1800 ◽  
Author(s):  
Gabriela P. Finkielstain ◽  
Patricia Forcinito ◽  
Julian C. K. Lui ◽  
Kevin M. Barnes ◽  
Rose Marino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Pattern ◽  
Somatic Growth ◽  
Postnatal Growth ◽  
Genetic Program ◽  
Male Rats ◽  
Postnatal Life ◽  
Multiple Organs ◽  
Organ Specific ◽  
Parenchymal Cells

Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified more than 1600 genes that were regulated with age (1 vs. 4 wk) coordinately in kidney, lung, and heart of male mice, including many genes that regulate proliferation. As examples, we focused on three growth-promoting genes, Igf2, Mest, and Peg3, that were markedly down-regulated with age. In situ hybridization revealed that expression occurred in organ-specific parenchymal cells and suggested that the decreasing expression with age was due primarily to decreased expression per cell rather than a decreased number of expressing cells. The declining expression of these genes was slowed during hypothyroidism and growth inhibition (induced by propylthiouracil at 0–5 wk of age) in male rats, suggesting that the normal decline in expression is driven by growth rather than by age per se. We conclude that there exists an extensive genetic program occurring during postnatal life. Many of the involved genes are regulated coordinately in multiple organs, including many genes that regulate cell proliferation. At least some of these are themselves apparently regulated by growth, suggesting that, in the embryo, a gene expression pattern is established that allows for rapid somatic growth of multiple tissues, but then, during postnatal life, this growth leads to negative-feedback changes in gene expression that in turn slow and eventually halt somatic growth, thus imposing a fundamental limit on adult body size.

scholarly journals Intravaginal Immunization of Mice with Recombinant Salmonella enterica Serovar Typhimurium Expressing Human Papillomavirus Type 16 Antigens as a Potential Route of Vaccination against Cervical Cancer

2008 ◽  
Vol 76 (5) ◽  
pp. 1940-1951 ◽  
Author(s):  
Hakim Echchannaoui ◽  
Matteo Bianchi ◽  
David Baud ◽  
Martine Bobst ◽  
Jean-Christophe Stehle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Immune Responses ◽  
Tumor Cells ◽  
Salmonella Enterica ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Wide Range ◽  
Serovar Typhimurium

ABSTRACT Cervical cancer, the second leading cause of cancer deaths in women, is the consequence of high-risk human papillomavirus (HPV) infections. Toward the development of therapeutic vaccines that can induce both innate and adaptive mucosal immune responses, we analyzed intravaginal (ivag) vaccine delivery of live attenuated Salmonella enterica serovar Typhimurium expressing HPV16L1 as a model antigen. Innate immune responses were examined in cervicovaginal tissues by determining gene expression patterns by microarray analysis using nylon membranes imprinted with cDNA fragments coding for inflammation-associated genes. At 24 h, a wide range of genes, including those for chemokines and Th1- and Th2-type cytokine and chemokine receptors were up-regulated in mice ivag immunized with Salmonella compared to control mice. However, the majority of transcripts returned to their steady-state levels 1 week after immunization, suggesting a transient inflammatory response. Indeed, cervicovaginal histology of immunized mice showed a massive, but transient, infiltration of macrophages and neutrophils, while T cells were still increased after 7 days. Ivag immunization also induced humoral and antitumor immune responses, i.e., serum and vaginal anti-HPV16VLP antibody titers similar to those induced by oral immunization, and significant protection in tumor protection experiments using HPV16-expressing C3 tumor cells. These results show that ivag immunization with live attenuated Salmonella expressing HPV16 antigens modulates the local mucosal gene expression pattern into a transient proinflammatory profile, elicits strong systemic and mucosal immunity against HPV16, and confers protection against HPV16 tumor cells subcutaneously implanted in mice. Examination of the efficacy with which ivag HPV16E7E6 Salmonella induces regression of tumors located in cervicovaginal tissue is warranted.

Crustacean (malacostracan) Hox genes and the evolution of the arthropod trunk

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2239-2249 ◽  
Author(s):  
A. Abzhanov ◽  
T.C. Kaufman
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
The Body ◽  
Ancestral State ◽  
Porcellio Scaber ◽  
Hox Gene ◽  
Overlapping Domains ◽  
Discrete Domains

Representatives of the Insecta and the Malacostraca (higher crustaceans) have highly derived body plans subdivided into several tagma, groups of segments united by a common function and/or morphology. The tagmatization of segments in the trunk, the part of the body between head and telson, in both lineages is thought to have evolved independently from ancestors with a distinct head but a homonomous, undifferentiated trunk. In the branchiopod crustacean, Artemia franciscana, the trunk Hox genes are expressed in broad overlapping domains suggesting a conserved ancestral state (Averof, M. and Akam, M. (1995) Nature 376, 420–423). In comparison, in insects, the Antennapedia-class genes of the homeotic clusters are more regionally deployed into distinct domains where they serve to control the morphology of the different trunk segments. Thus an originally Artemia-like pattern of homeotic gene expression has apparently been modified in the insect lineage associated with and perhaps facilitating the observed pattern of tagmatization. Since insects are the only arthropods with a derived trunk tagmosis tested to date, we examined the expression patterns of the Hox genes Antp, Ubx and abd-A in the malacostracan crustacean Porcellio scaber (Oniscidae, Isopoda). We found that, unlike the pattern seen in Artemia, these genes are expressed in well-defined discrete domains coinciding with tagmatic boundaries which are distinct from those of the insects. Our observations suggest that, during the independent tagmatization in insects and malacostracan crustaceans, the homologous ‘trunk’ genes evolved to perform different developmental functions. We also propose that, in each lineage, the changes in Hox gene expression pattern may have been important in trunk tagmatization.

scholarly journals The role of oligosaccharides and polysaccharides of xylan and mannan in gut health of monogastric animals

2020 ◽  
Vol 9 ◽  
Author(s):  
Utsav P. Tiwari ◽  
Stephen A. Fleming ◽  
Muhammed S. Abdul Rasheed ◽  
R. Jha ◽  
Ryan N. Dilger
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Modulation ◽  
The Body ◽  
Gut Health ◽  
Gi Tract ◽  
Immune Organ ◽  
Feed Ingredient ◽  
Cereal Grain

Abstract Apart from its role as a digestive and absorptive organ, the gastrointestinal (GI) tract is a vital immune organ that encompasses roughly 70 % of the total immune cells of the body. As such, the physical, chemical and nutrient composition of the diet influences overall GI function, effectively as an immune organ. With the improvement in feed technology, agro-industrial co-products that are high in fibre have been widely used as a feed ingredient in the diets of pigs and poultry. Arabinoxylan (AX) and mannan are the most abundant hemicellulosic polysaccharides present in cereal grain and co-product ingredients used in the livestock industry. When monogastric animals consume diets containing high amounts of AX and mannans, stimulation of GI immune cells may occur. This involves the activation of several cellular and molecular pathways of the immune system and requires a considerable amount of energy and nutrients to be expended by the animal, which may ultimately influence overall health and growth performance of animals. Therefore, a better understanding of the role of AX and mannan in immune modulation will be helpful in modulating untoward GI immune responses, thereby minimising nutrient and energy expenditure toward this effort. This review will summarise pertinent research on the role of oligosaccharides and polysaccharides containing AX and mannans in immune modulation in order to preserve gut integrity.

scholarly journals Macrophages and the maintenance of homeostasis

2020 ◽  
Author(s):  
David M. Mosser ◽  
Kajal Hamidzadeh ◽  
Ricardo Goncalves
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Macrophage Polarization ◽  
The Body ◽  
Sensory Stimuli ◽  
Cellular Processes ◽  
Wide Range ◽  
Tissue Responses ◽  
Different Response

Abstract There have been many chapters written about macrophage polarization. These chapters generally focus on the role of macrophages in orchestrating immune responses by highlighting the T-cell-derived cytokines that shape these polarizing responses. This bias toward immunity is understandable, given the importance of macrophages to host defense. However, macrophages are ubiquitous and are involved in many different cellular processes, and describing them as immune cells is undoubtedly an oversimplification. It disregards their important roles in development, tissue remodeling, wound healing, angiogenesis, and metabolism, to name just a few processes. In this chapter, we propose that macrophages function as transducers in the body. According to Wikipedia, “A transducer is a device that converts energy from one form to another.” The word transducer is a term used to describe both the “sensor,” which can interpret a wide range of energy forms, and the “actuator,” which can switch voltages or currents to affect the environment. Macrophages are able to sense a seemingly endless variety of inputs from their environment and transduce these inputs into a variety of different response outcomes. Thus, rather than functioning as immune cells, they should be considered more broadly as cellular transducers that interpret microenvironmental changes and actuate vital tissue responses. In this chapter, we will describe some of the sensory stimuli that macrophages perceive and the responses they make to these stimuli to achieve their prime directive, which is the maintenance of homeostasis.

scholarly journals Identification and Validation of Gene Expression Pattern and Signature in Patients with Immune Thrombocytopenia

2016 ◽  
Vol 22 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Qi-dong Ye ◽  
Hui Jiang ◽  
Xue-lian Liao ◽  
Kai Chen ◽  
Shan-shan Li
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Immune Thrombocytopenia ◽  
Type I Diabetes ◽  
Gene Expression Pattern ◽  
Enrichment Analysis ◽  
Interferon Γ ◽  
Gene Set Enrichment Analysis ◽  
Type I ◽  
Healthy Humans

In the present study, we sought to define genes associated with immune thrombocytopenia (ITP). Microarray analysis revealed that of 1002 genes associated with ITP, 309 genes had downregulated expression and 693 genes had upregulated expression in patients with ITP. Gene set enrichment analysis revealed that 11 pathways were positively correlated to ITP, such as type I diabetes mellitus, intestinal immune network for IgA production, and oxidative phosphorylation. The messenger RNA expression levels of the indicated genes, including HLA-DRB5, IGHV3-66, IFI27, FAM212A, PLD5, tumor necrosis factor (TNF)–α, interferon-γ, interleukin (IL)–1β, and IL-4, were significantly increased in patients with ITP compared with healthy humans, while MMP8, SLC1A3, CRISP3, THBS1, FMN1, and IL-10 were decreased. In conclusion, the gene expression profile of patients with ITP has established a foundation to study the gene mechanism of ITP progression.

scholarly journals CREB-binding protein gene, HAC701, negatively regulates WRKY45-dependent immunity in rice

2020 ◽  
Author(s):  
Nino A. Espinas ◽  
Tu Ngoc Le ◽  
Miura Saori ◽  
Yasuka Shimajiri ◽  
Ken Shirasu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Binding Protein ◽  
Large Set ◽  
Sequencing Analysis ◽  
Creb Binding Protein ◽  
Transcriptional Coactivator ◽  
Wild Type ◽  
Genome Wide ◽  
H3k9 Acetylation

ABSTRACTCREB-binding protein (CBP) is a known transcriptional coactivator and an acetyltransferase that functions in several cellular processes by regulating gene expression. However, how it functions in plant immunity remains unexplored. By characterizing hac701, we demonstrate that HAC701 negatively regulates the immune responses in rice. hac701 shows enhanced disease resistance against a bacterial pathogen, Pseudomonas syringae pv. oryzae (Pso), which causes bacterial halo blight of rice. Our transcriptomic analysis revealed that rice WRKY45, one of the main regulators of rice immunity, is upregulated in hac701 and possibly conferring the resistance phenotype against Pso. The morphological phenotypes of hac701 single mutants were highly similar to WRKY45 overexpression transgenic lines reported in previous studies. In addition, we also compared the list of genes in these studies when WRKY45 is overexpressed and chemically induced transiently with the differentially expressed genes (DEGs) in hac701, and found that they largely overlap. When we investigated for cis-elements found 1kb upstream of WRKY45 gene and WRKY45-dependent DEGs, we found that WRKY45 promoter contains the CRE motif, a possible target of HAC701-mediated regulation. Genome-wide H3K9 acetylation profiling showed depletion of acetylation at large set of genes in hac701. However, consistent with the upregulation of WRKY45 gene expression, our ChIP-sequencing analysis demonstrated that regions of WRKY45 promoter are enriched in H3K9 acetylation in hac701 compared to the segregated wild type control in the mock condition. WRKY45 promoter might be on the receiving end for possible genome-wide compensatory effects when a global regulator like HAC701 is mutated. Finally, we show that HAC701 may have roles in systemic immune signaling. We therefore propose that wild type HAC701 negatively regulates WRKY45 gene expression, thereby suppressing immune responses.SIGNIFICANCEHAC701 is a member of CREB-binding protein (CBP) family that acts as transcriptional coactivator and acetyltransferase. However, little is known how it regulates innate immunity in plants. Herein we reported that rice HAC701 suppresses WRKY45-dependent defense pathway. Our study showed that HAC701 seemingly interacts genetically with WRKY45 in rice to modulate immune responses against pathogens.

scholarly journals Protease profile of normal and neoplastic mast cells in the human bone marrow

2020 ◽  
Author(s):  
Dmitri Atiakshin ◽  
Igor Buchwalow ◽  
Peter Horny ◽  
Markus Tiemann
Keyword(s):  
Bone Marrow ◽  
Targeted Therapy ◽  
Mast Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Human Bone ◽  
Secretory Pathways ◽  
Organ Specific ◽  
Detailed Assessment

Abstract Mast cells (MC) are immune cells that produce a variety of mediators, such as proteases, that are important in the body’s immune responses. MC proteases have pronounced multifunctionality and in many respects determine the biological characteristics of the organ-specific MC population. Although, increased numbers of MC are one of the objective mastocytosis signs, a detailed assessment of the proteases biogenesis and excretion mechanisms in the bone marrow has not yet been carried out. Here, we performed an analysis of the expression of proteases in patients with various forms of mastocytosis. We presented data on intracellular protease co-localization in the bone marrow MCs and discussed their implication in secretory pathways of MCs in the development of the disease. Characterization of MC proteases expression during mastocytosis can be used to refine the MC classification, make a prognosis, and increase the effectiveness of targeted therapy.

scholarly journals Protease profile of normal and neoplastic mast cells in the human bone marrow with special emphasis on systemic mastocytosis

2021 ◽  
Author(s):  
Dmitri Atiakshin ◽  
Igor Buchwalow ◽  
Peter Horny ◽  
Markus Tiemann
Keyword(s):  
Bone Marrow ◽  
Targeted Therapy ◽  
Mast Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Systemic Mastocytosis ◽  
Secretory Pathways ◽  
Organ Specific ◽  
Detailed Assessment

AbstractMast cells (MC) are immune cells that produce a variety of mediators, such as proteases, that are important in the body’s immune responses. MC proteases have pronounced multifunctionality and in many respects determine the biological characteristics of the organ-specific MC population. Although, increased numbers of MC are one of the objective mastocytosis signs, a detailed assessment of the proteases biogenesis and excretion mechanisms in the bone marrow (BM) has not yet been carried out. Here, we performed an analysis of the expression of proteases in patients with various forms of systemic mastocytosis. We presented data on intracellular protease co-localization in human BM MCs and discussed their implication in secretory pathways of MCs in the development of the disease. Systemic mastocytosis, depending on the course, is featured by the formation of definite profiles of specific proteases in various forms of atypical mast cells. Intragranular accumulation of tryptase, chymase and carboxypeptidases in the hypochromic phenotype of atypical mast cells is characterized. Characterization of MC proteases expression during mastocytosis can be used to refine the MC classification, help in a prognosis, and increase the effectiveness of targeted therapy.

scholarly journals Dynamic Maternal Gradients Control Timing and Shift-Rates forDrosophilaGap Gene Expression

2016 ◽  
Author(s):  
Berta Verd ◽  
Anton Crombach ◽  
Johannes Jaeger
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Drosophila Melanogaster ◽  
Pattern Formation ◽  
Dynamic Process ◽  
Gene Expression Pattern ◽  
The Body ◽  
Transient Dynamics ◽  
Gap Gene ◽  
Gap Genes

AbstractPattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network inDrosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded bybicoid (bcd)andcaudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development.Author SummaryAnimal development is a highly dynamic process. Biochemical or environmental signals can cause the rules that shape it to change over time. We know little about the effects of such changes. For the sake of simplicity, we usually leave them out of our models and experimental assays. Here, we do exactly the opposite. We characterise precisely those aspects of pattern formation caused by changing signalling inputs to a gene regulatory network, the gap gene system ofDrosophila melanogaster. Gap genes are involved in determining the body segments of flies and other insects during early development. Gradients of maternal morphogens activate the expression of the gap genes. These gradients are highly dynamic themselves, as they decay while being read out. We show that this decay controls the peak concentration of gap gene products, produces smooth boundaries of gene expression, and slows down the observed positional shifts of gap domains in the posterior of the embryo, thereby stabilising the spatial pattern. Our analysis demonstrates that the dynamics of gene regulation not only affect the timing, but also the positioning of gene expression. This suggests that we must pay closer attention to transient dynamic aspects of development than is currently the case.

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