The physiology of immune evasion during pregnancy; the critical role of placental tryptophan metabolism and transport

2001 ◽  
Vol 442 (5) ◽  
pp. 639-641 ◽  
Author(s):  
Kudo Y. ◽  
Boyd C.
Keyword(s):  
Immune Evasion ◽  
Critical Role ◽  
Tryptophan Metabolism

scholarly journals Insights into the mysterious genetic variation profile oftprKinTreponema pallidumunder the development of natural human syphilis infection

2019 ◽  
Author(s):  
Dan Liu ◽  
Man-Li Tong ◽  
Yong Lin ◽  
Li-Li Liu ◽  
Li-Rong Lin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Immune Evasion ◽  
High Frequency ◽  
Critical Role ◽  
Treponema Pallidum ◽  
Secondary Syphilis ◽  
Human Infection ◽  
Amino Acid Sequences ◽  
Potential Vaccine

AbstractAlthough the variations of thetprKgene inTreponema pallidumwere considered to play a critical role in the pathogenesis of syphilis, how actual variable characteristics oftprKin the course of natural human infection enabling the pathogen’s survive has thus far remained unclear. Here, we performed NGS to investigatetprKofT. pallidumdirectly from primary and secondary syphilis samples. Compared with diversity intprKof the strains from primary syphilis samples, there were more mixture variants found within seven V regions of thetprKgene among the strains from secondary syphilis samples, and the frequencies of predominant sequences within V regions oftprKwere generally decreased (less than 80%) with the proportion of minor variants in 10-60% increasing. Noteworthy, the variations within V regions oftprKalways obeyed a strict 3 bp changing pattern. AndtprKin the strains from the two-stage samples kept some stable amino acid sequences within V regions. Particularly, the amino acid sequences IASDGGAIKH and IASEDGSAGNLKH in V1 not only presented a high proportion of inter-population sharing, but also presented a relatively high frequency (above 80%) in the populations. Besides,tprKalways demonstrated remarkable variability in V6 at both the intra- and inter-strain levels regardless of the course. These findings unveiled that the different profile oftprK in T. pallidumdirectly from primary and secondary syphilis samples, indicating that throughout the development of syphilisT. pallidumconstantly varies its domaintprKgene to obtain the best adaptation to the host. While this changing was always subjected a strict gene conversion mechanism to keep an abnormal TprK. The highly stable peptides found in V1 would probably be promising potential vaccine components. And the highly heterogenetic regions (e.g. V6) could provide insight into the mysterious role oftprKin immune evasion.Author summaryAlthough the variations of thetprKgene inTreponema pallidumwere considered to play a critical role in the pathogenesis of syphilis, how actual variable characteristics oftprKin the course of natural human infection enabling the pathogen’s survive has thus far remained unclear. Here, we performed next-generation sequencing, a more sensitive and reliable approach, to investigatetprKofTreponema pallidumdirectly from primary and secondary syphilis patients, revealing that the profile oftprKinT. pallidumfrom the two-stage samples was different. Within the strains from secondary syphilis patients, more mixture variants within seven V regions oftprKwere found, the frequencies of their predominant sequences were generally decreased with the proportion of minor variants in 10-60% was increased. And the variations within V regions oftprKalways obeyed a strict 3 bp changing pattern. Noteworthy, the amino acid sequences IASDGGAIKH and IASEDGSAGNLKH in V1 presented a high proportion of inter-population sharing and presented a relatively high frequency in the populations. And V6 region always demonstrated remarkable variability at intra- and inter-patient levels regardless of the course. These findings provide insights into the mysterious role of TprK in immune evasion and for further exploring the potential vaccine components.

scholarly journals Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Peng-Fei Zhang ◽  
Xu Pei ◽  
Ke-Sang Li ◽  
Li-Na Jin ◽  
Fei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Evasion ◽  
Critical Role ◽  
Circular Rna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment. Methods The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p. Results Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy. Conclusion Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.

scholarly journals A40 INTESTINAL EPITHELIAL NCOR1 TARGETS TRYPTOPHAN METABOLISM AND PROTECTS AGAINST EXPERIMENTAL COLITIS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 48-49
Author(s):  
M Lecours ◽  
A Di Castro ◽  
V Reyes-Nicolas ◽  
S St-Jean ◽  
A Loiselle ◽  
...  
Keyword(s):  
Target Genes ◽  
Gastrointestinal Disease ◽  
Critical Role ◽  
Experimental Colitis ◽  
Tryptophan Metabolism ◽  
Gene Profiling ◽  
Intestinal Epithelial ◽  
Tryptophan Degradation ◽  
And Control

Abstract Background The nuclear co-repressor NCOR1 is a central protein that orchestrates the assembly of a large transcriptional repression complex. NCOR1 controls activation of macrophages by repressing a large variety of pro-inflammatory genes. Aims We aimed to investigate the role of intestinal epithelial NCOR1 during experimental colitis. Methods Conditional deletion of Ncor1 in the whole intestinal epithelium was achieved by crossing Villin-Cre and Ncor1loxP/loxP C57BL/6 mouse models. A gene profiling analysis in the colon of non-diseased NCOR1ΔIEC and control mice was performed. NCOR1ΔIEC and control littermate mice were treated with dextran sulfate sodium (DSS) in drinking water. Results DSS-induced colitis in NCOR1ΔIEC mice was more severe than control mice according to survival as well as clinical observations. A statistical analysis predicted 85 unique and mapped transcripts being significantly modulated between NCOR1ΔIEC and control mice. An Ingenuity Pathway Analysis from these predicted target genes identified gastrointestinal disease (79 transcripts) as top disease and biofunction. Analysis of enriched targets in specific canonical pathways predicted an increase in the tryptophan degradation pathway (P = 3.2E-02), a pathway recently demonstrated to be strongly relevant to inflammatory bowel disease severity. Indoleamine-pyrrole 2,3-dioxygenase (IDO1), that catalyzes the first and rate-limiting step of tryptophan oxidation, was induced more than 7 times in the colon of NCOR1ΔIEC mice. Induction of Ido1 was also confirmed in cultured ex vivo colon organoids deleted for Ncor1. Conclusions Our results highlight the critical role of NCOR1 to maintain intestinal inflammatory homeostasis during experimental colitis and uncover a novel function for NCOR1 in the regulation of Ido1 expression and potentially tryptophan metabolism. Funding Agencies CIHR

scholarly journals Low neoantigen expression and poor T cell priming underlie early immune escape in cancer

2020 ◽  
Author(s):  
Peter Westcott ◽  
Nathan Sacks ◽  
Jason Schenkel ◽  
Olivia Smith ◽  
Daniel Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Evasion ◽  
Immune Escape ◽  
Critical Role ◽  
Immune Surveillance ◽  
Tumor Rejection ◽  
Variable Expression ◽  
High Affinity ◽  
T Cell Priming

Abstract Immune evasion is a hallmark of cancer, and therapies that restore immune surveillance have proven highly effective in cancers with high tumor mutation burden (TMB) (e.g. microsatellite instable (MSI) colorectal cancer (CRC)). Whether low TMB cancers, which are largely refractory to immunotherapy, harbor T cell neoantigens capable of engaging adaptive immunity remains unclear. Here, we show that the majority of microsatellite stable (MSS) CRC harbors predicted high-affinity neoantigens despite low TMB. Unexpectedly, these neoantigens are broadly expressed at lower levels relative to those in MSI CRC, suggesting a potential role of antigen expression in tumor immune surveillance. To test this, we developed a versatile platform for functional interrogation of neoantigens with variable expression and applied it to novel preclinical colonoscopy-guided mouse models of CRC. While high expression of multiple high-affinity MHC-I-restricted neoantigens universally resulted in tumor rejection, low expression resulted in poor T cell priming and tumor progression. Strikingly, experimental or therapeutic rescue of priming rendered T cells fully capable of controlling tumors with low neoantigen expression. These findings underscore a critical role of neoantigen expression levels in immune evasion and suggest that poor expression or presentation may be a general feature of neoantigens acquired early in tumorigenesis. Finally, poorly expressed neoantigens, commonly excluded in tumor vaccine pipelines, may hold untapped therapeutic potential.

scholarly journals A critical role of non-classical MHC in tumor immune evasion in the amphibian Xenopus model

2014 ◽  
Vol 35 (8) ◽  
pp. 1807-1813 ◽  
Author(s):  
Nikesha Haynes-Gilmore ◽  
Maureen Banach ◽  
Eva-Stina Edholm ◽  
Edith Lord ◽  
Jacques Robert
Keyword(s):  
Immune Evasion ◽  
Critical Role ◽  
Tumor Immune Evasion

scholarly journals FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer

2021 ◽  
Vol 22 (1) ◽  
pp. 455
Author(s):  
Kayla Bastian ◽  
Emma Scott ◽  
David J. Elliott ◽  
Jennifer Munkley
Keyword(s):  
Immune Evasion ◽  
Tumour Progression ◽  
Critical Role ◽  
Critical Factor ◽  
Cancer Therapeutics ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Α3β1 Integrin ◽  
Universal Feature ◽  
Core Fucosylation

Aberrant glycosylation is a universal feature of cancer cells that can impact all steps in tumour progression from malignant transformation to metastasis and immune evasion. One key change in tumour glycosylation is altered core fucosylation. Core fucosylation is driven by fucosyltransferase 8 (FUT8), which catalyses the addition of α1,6-fucose to the innermost GlcNAc residue of N-glycans. FUT8 is frequently upregulated in cancer, and plays a critical role in immune evasion, antibody-dependent cellular cytotoxicity (ADCC), and the regulation of TGF-β, EGF, α3β1 integrin and E-Cadherin. Here, we summarise the role of FUT8 in various cancers (including lung, liver, colorectal, ovarian, prostate, breast, melanoma, thyroid, and pancreatic), discuss the potential mechanisms involved, and outline opportunities to exploit FUT8 as a critical factor in cancer therapeutics in the future.

The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

2008 ◽  
Vol 15 (2) ◽  
pp. 50-59 ◽  
Author(s):  
Amy Philofsky
Keyword(s):  
Language Development ◽  
Critical Role ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Children With Asd ◽  
Prevalence Estimates ◽  
Notable Increase ◽  
Screening Assessment ◽  
Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

A critical role of iNOS-derived Nitric Oxide (NO) and progesterone in implantation

1998 ◽  
Vol 5 (1) ◽  
pp. 115A-115A
Author(s):  
K CHWALISZ ◽  
E WINTERHAGER ◽  
T THIENEL ◽  
R GARFIELD
Keyword(s):  
Nitric Oxide ◽  
Critical Role
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