scholarly journals Identification of Regulatory Functions of LncRNAs Associated With T. circumcincta Infection in Adult Sheep

2021 ◽  
Vol 12 ◽  
Author(s):  
Praveen Krishna Chitneedi ◽  
Rosemarie Weikard ◽  
Juan J. Arranz ◽  
María Martínez-Valladares ◽  
Christa Kuehn ◽  
...  
Keyword(s):  
Immune Response ◽  
Functional Role ◽  
Defense Mechanism ◽  
Nematode Infection ◽  
Cellular Growth ◽  
Differentially Expressed ◽  
Differential Host ◽  
Adult Sheep ◽  
Gene Enrichment

Several recent studies have demonstrated the role of long non-coding RNAs (lncRNAs) in regulating the defense mechanism against parasite infections, but no studies are available that investigated their relevance for immune response to nematode infection in sheep. Thus, the aim of the current study was to (i) detect putative lncRNAs that are expressed in the abomasal lymph node of adult sheep after an experimental infection with the gastrointestinal nematode (GIN) Teladorsagia circumcincta and (ii) to elucidate their potential functional role associated with the differential host immune response. We hypothesized that putative lncRNAs differentially expressed (DE) between samples from animals that differ in resistance to infection may play a significant regulatory role in response to nematode infection in adult sheep. To obtain further support for our hypothesis, we performed co-expression and functional gene enrichment analyses with the differentially expressed lncRNAs (DE lncRNAs). In a conservative approach, we included for this predictive analysis only those lncRNAs that are confirmed and supported by documentation of expression in gastrointestinal tissues in the current sheep gene atlas. We identified 9,105 putative lncRNA transcripts corresponding to 7,124 gene loci. Of these, 457 were differentially expressed lncRNA loci (DELs) with 683 lncRNA transcripts. Based on a gene co-expression analysis via weighted gene co-expression network analysis, 12 gene network modules (GNMs) were found significantly correlated with at least one of 10 selected target DE lncRNAs. Based on the principle of “guilt-by-association,” the DE genes from each of the three most significantly correlated GNMs were subjected to a gene enrichment analysis. The significant pathways associated with DE lncRNAs included ERK5 Signaling, SAPK/JNK Signaling, RhoGDI Signaling, EIF2 Signaling, Regulation of eIF4 and p70S6K Signaling and Oxidative Phosphorylation pathways. They belong to signaling pathway categories like Cellular Growth, Proliferation and Development, Cellular Stress and Injury, Intracellular and Second Messenger Signaling and Apoptosis. Overall, this lncRNA study conducted in adult sheep after GIN infection provided first insights into the potential functional role of lncRNAs in the differential host response to nematode infection.

scholarly journals Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

2020 ◽  
Vol 21 (21) ◽  
pp. 8289
Author(s):  
Mari T. Kaartinen ◽  
Mansi Arora ◽  
Sini Heinonen ◽  
Aila Rissanen ◽  
Jaakko Kaprio ◽  
...  
Keyword(s):  
Immune Response ◽  
Adipose Tissue ◽  
Family Members ◽  
Enrichment Analysis ◽  
Human Adipose Tissue ◽  
Adipocyte Size ◽  
Gene Enrichment ◽  
Adipocyte Hypertrophy ◽  
Mz Twins

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.

Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis

Gut ◽  
2019 ◽  
Vol 68 (8) ◽  
pp. 1477-1492 ◽  
Author(s):  
Lijun Liao ◽  
Kai Markus Schneider ◽  
Eric J C Galvez ◽  
Mick Frissen ◽  
Hanns-Ulrich Marschall ◽  
...  
Keyword(s):  
Immune Response ◽  
Liver Injury ◽  
Sclerosing Cholangitis ◽  
Functional Role ◽  
Innate Immune ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Intestinal Dysbiosis ◽  
Nlrp3 Inflammasome Activation

ObjectiveThere is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated the functional role of gut–liver crosstalk for CLD in the murine Mdr2 knockout (Mdr2−/−) model resembling human primary sclerosing cholangitis (PSC).DesignMale Mdr2−/−, Mdr2−/− crossed with hepatocyte-specific deletion of caspase-8 (Mdr2−/−/Casp8∆hepa) and wild-type (WT) control mice were housed for 8 or 52 weeks, respectively, to characterise the impact of Mdr2 deletion on liver and gut including bile acid and microbiota profiling. To block caspase activation, a pan-caspase inhibitor (IDN-7314) was administered. Finally, the functional role of Mdr2−/−-associated intestinal dysbiosis was studied by microbiota transfer experiments.ResultsMdr2−/− mice displayed an unfavourable intestinal microbiota signature and pronounced NLRP3 inflammasome activation within the gut–liver axis. Intestinal dysbiosis in Mdr2−/− mice prompted intestinal barrier dysfunction and increased bacterial translocation amplifying the hepatic NLRP3-mediated innate immune response. Transfer of Mdr2−/− microbiota into healthy WT control mice induced significant liver injury in recipient mice, highlighting the causal role of intestinal dysbiosis for disease progression. Strikingly, IDN-7314 dampened inflammasome activation, ameliorated liver injury, reversed serum bile acid profile and cholestasis-associated microbiota signature.ConclusionsMDR2-associated cholestasis triggers intestinal dysbiosis. In turn, translocation of endotoxin into the portal vein and subsequent NLRP3 inflammasome activation contribute to higher liver injury. This process does not essentially depend on caspase-8 in hepatocytes, but can be blocked by IDN-7314.

The functional role of spleen neutrophil-like cells in the immune response to allogeneic tumor cells

2007 ◽  
Vol 414 (1) ◽  
pp. 242-245 ◽  
Author(s):  
E. V. Maryukhnich ◽  
E. S. Zvezdova ◽  
T. V. Anfalova ◽  
L. M. Khromykh ◽  
D. B. Kazansky
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Functional Role ◽  
Allogeneic Tumor

scholarly journals Genome Wide Transcriptomic Analysis Identifies Dysregulated Splicing Factor Profile with Molecular and Functional Role in Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 361-361 ◽  
Author(s):  
Anil Aktas Samur ◽  
Mehmet Kemal Samur ◽  
Michael A Lopez ◽  
Sanika Derebail ◽  
Kenneth C. Anderson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Alternative Splicing ◽  
Research Funding ◽  
Functional Role ◽  
Molecular Mechanisms ◽  
Differentially Expressed ◽  
Alternate Splicing ◽  
Genome Wide ◽  
Splicing Pattern

Alternative splicing (AS) is a critical post-transcriptional event, which affects the number of cellular processes. Aberrant splicing of some genes has been reported in multiple myeloma (MM). However, to date, whole-transcriptome-wide AS study has not been performed. We used deep RNA-sequencing data from 16 normal plasma cells (NPC) and 360 newly-diagnosed MM patients to describe the landscape of the alternative splicing events and the molecular mechanisms driving aberrant AS in MM. Global splicing analysis showed that mutually exclusive exon (MXE) (n=510) and Skipped Exon (SE) (n=417) are the most frequent splicing events in MM compared to NPC. Among these events, ~54% were observed in genes which are not differentially expressed between MM and NPC and 46% of the AS events (SE, MXE, retained intron, alternative 3'/5' sites) were observed in differentially expressed genes targeting 203 unique genes. AS affected RNA transcription regulation genes such as IKZF1, IKZF3, and key regulatory elements in MM including, IRF3, IRF4, or key transcription factors such as MEF2C, XPB1, STAT2, and ILF3. In general, AS targetted DNA replication, cell cycle, and apoptosis pathways. MM subgroups showed a heterogeneity for AS events. Monosomy 14, t(4;14), del1p and del17p had the highest number of unique (not observed in other subgroups) AS events compared to NPC.To understanding the molecular mechanisms driving aberrant alternate splicing we next investigated115 splicing factors (SF) in MM and associated them with AS events. We observed that ~40% of SF were dysregulated (dysregulated expression and/or copy number alteration) in MM compared to NPC, including SRSF, PCBP and RBM families. To understand the key binding regions, we have performed SF binding motif enrichment analysis around AS events and found that SRFS1, SRSF9, and PCB1 motifs to be enriched among the splicing events. Importantly, SRSF1 expression was linked with survival in two independent MM datasets.We therefore explored functional role of SRSF1 in MM with perturbation studies. While upregulation of SRSF1 expression significantly increased the cell growth and survival, conversely downregulation of SRSF1 inhibited the both. To dissect the mechanisms of SRSF1-mediated MM growth induction, we utilized SRSF1 mutants lacking either of the 2 RNA-recognition motifs or the serine/argine-rich C-terminal domain involved in protein-protein interactions, and recruitment of spliceosome components. We also utilized a C-terminal fusion of SRSF1 with the nuclear-retention signal of SRSF2 (NRS1 mutant), to force SRSF1 retention in the nucleus and assess the role of its nuclear versus cytoplasmic functions. These studies suggested that SRSF1-regulated AS effects MM cell proliferation. We surprisingly also found that even NRS1 mutant failed to promote MM growth, suggesting an important role of cytoplasmic SRSF1 in promoting MM cells proliferation.We next investigated alternative splicing pattern changes induced by SRSF1 knock down.When analyzing cellular functions of SRSF1-regulated splicing events, we found that SRSF1 knock down affect's genes in the RNA processing pathway as well as genes involved in cancer-related functions such as mTOR, E2F and MYC-related pathways. Splicing analysis was corroborated with immunoprecipitation (IP) followed by mass spectrometry (MS) analysis of T7-tagged SRSF1 MM cells.Finally, using genome wide chromatin and transcription landscape mapping techniques, we have found SRSF1 to be under the transcriptional control of oncogenic E2F1 in MM cells. Consistent with these findings, we observed greater in vitro loss of viability in a large panel of MM cell lines compared with PBMCs from healthy volunteers, following exposure to the splicing modulator pladeniolide. In summary, this study for the first time reports a detailed splicing landscape in myeloma and highlights the biological and clinical importance of alternative splicing events. Moreover, these results indicate a functional role and clinical significance of a gene involved in regulation of alternate splicing in MM, highlighting the need to further understand the splicing pattern in myeloma initiation and progression. Disclosures Anderson: Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Oncopep: Other: Scientific Founder; Sanofi-Aventis: Other: Advisory Board; Bristol-Myers Squibb: Other: Scientific Founder. Avet-Loiseau:takeda: Consultancy, Other: travel fees, lecture fees, Research Funding; celgene: Consultancy, Other: travel fees, lecture fees, Research Funding. Munshi:Adaptive: Consultancy; Abbvie: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Oncopep: Consultancy; Amgen: Consultancy; Celgene: Consultancy.

scholarly journals Cell therapy for Parkinson׳s disease: Functional role of the host immune response on survival and differentiation of dopaminergic neuroblasts

2016 ◽  
Vol 1638 ◽  
pp. 15-29 ◽  
Author(s):  
Shirley D. Wenker ◽  
María Celeste Leal ◽  
María Isabel Farías ◽  
Xianmin Zeng ◽  
Fernando J. Pitossi
Keyword(s):  
Immune Response ◽  
Cell Therapy ◽  
Functional Role ◽  
Host Immune Response

scholarly journals Identification of differentially expressed genes for fescue toxicosis in high and low tolerant Angus cows

2019 ◽  
Author(s):  
Piush Khanal ◽  
Leticia P Sanglard ◽  
Kyle Mayberry ◽  
Jeffery Sommer ◽  
Matthew H Poore ◽  
...  
Keyword(s):  
Immune Response ◽  
Differentially Expressed Genes ◽  
Gene Networks ◽  
Cardiovascular Function ◽  
Cellular Growth ◽  
Differentially Expressed ◽  
Fescue Toxicosis ◽  
Biological Processes ◽  
Q Value ◽  
Beef Industry

Abstract Background Fescue toxicosis (FT) is the multifaceted syndrome that causes the major loss of revenue in beef industry. Management of FT has been substantial challenge for the beef industry. Little research has been conducted to identify host genetic variation for FT response. Therefore, the objectives of this study were 1) to identify differentially expressed genes (DEG) in animals with contrasting response to fescue toxicosis, 2) to assess the biological relevance of DEG and 3) to investigate the relationships of DEG through gene networks in Angus cows. Results Genotype-by-location-by-time interaction was evident, with one location (2,296) having much greater number of DEG (q-value < 0.1) between HT and LT animals than the other (554). In addition, there was a greater number of DEG (q-value < 0.1) between HT and LT animals on week 5 (3,892) than on weeks 1(1,413), 9 (1,384), and 13 (573). So, further analyses focused on DEG between HT and LT animals on week 5 at the most toxic location. The most significant DEG between HT and LT animals had relevant functions associated with FT: cellular growth (SPDYC, HEYL, ANXA13), cardiovascular function (FGB, HBA, WNT11, BPIFB4, MESP2), protein metabolism (ENPP6, MMP8), and immune response (CTBS, SDC2, CXCL13, IL-13, JAKMIP2). The strongest positive partial correlation (0.99) was between CTBS and CXCL13, where CTBS is involved in carbohydrate metabolism and immune function, and CXCL13 is involved in immune, inflammatory, and defense response, and G-protein coupled pathway. The regulation of the most significant DEG between HT and LT animals on week 5 are highly correlated, indicating a complex interaction between. When all DEG were analyzed, the enriched biological processes associated with fescue toxicosis included immune response, cardiovascular function and development, metabolic, cellular and biological processes, and fertilization. Conclusions These findings provide potential biomarkers that should be evaluated for selection of cattle with greater tolerance to fescue toxicosis which will help to establish the herd with fescue tolerant cows in regions where high endophyte infected pasture is present.

scholarly journals Role of Macrophages in the Altered Epithelial Function during a Type 2 Immune Response Induced by Enteric Nematode Infection

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e84763 ◽  
Author(s):  
Luigi Notari ◽  
Diana C. Riera ◽  
Rex Sun ◽  
Jennifer A. Bohl ◽  
Leon P. McLean ◽  
...  
Keyword(s):  
Immune Response ◽  
Nematode Infection ◽  
Type 2 Immune Response

scholarly journals A SYSTEMATIC REVIEW: THE ASSOCIATION BETWEEN URINE LEUKOCYTES AND THE TYPES OF URINARY TRACT INFECTION

2022 ◽  
Vol 29 (1) ◽  
Author(s):  
Joshua Sunjaya ◽  
Sheella Rima Bororing ◽  
Maria Riastuti Iryaningrum
Keyword(s):  
Systematic Review ◽  
Immune Response ◽  
Functional Role ◽  
Normal Limit ◽  
Leukocyte Count ◽  
Innate Immune ◽  
Exclusion Criteria ◽  
Review Study ◽  
Age Range

Objective: This study aimed to determine the functional role of the urine leukocyte count on type of UTI. Material & Methods: This is a systematic review study with searches for articles from 2010-2020 through the PubMed, ProQuest, and EBSCO databases. The exclusion criteria in this study are patients using catheters (CAUTI), UTI patients in the Intensive Care Unit (ICU), and pediatric or infant patients. There were 1158 studies found and 3 studies synthesized. Results: There are 1130 patients studied. Age range from 18 to 89.1 years. Three studies showed that there was an association between the number of urinary leukocytes and the type of UTI (Tommaso Cai et al., p < 0.0001; and Alexander R. Levine et al., p < 0.001) and one study had no relationship. Conclusion: There is a relationship between the number of urinary leukocytes with the type of UTI. An increase in the number of urinary leukocytes above the normal limit is the sign of body’s immune response to eliminate uropathogens. The innate immune characteristic factors and the body’s immune response have an important role in causing symptoms in UTI patients.

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