Harnessing ADAR-Mediated Site-Specific RNA Editing in Immune-Related Disease: Prediction and Therapeutic Implications.

ADAR (Adenosine Deaminases Acting on RNA) proteins are a group of enzymes that play a vital role in RNA editing by converting adenosine to inosine in RNAs. This process is a frequent post-transcriptional event observed in metazoan transcripts. Recent studies indicate widespread dysregulation of ADAR-mediated RNA editing across many immune-related diseases, such as human cancer. We comprehensively review ADARs' function as pattern recognizers and their capability to contribute to mediating immune-related pathways. We also highlight the potential role of site-specific RNA editing in maintaining homeostasis and its relationship to various diseases, such as human cancers. More importantly, we summarize the latest cutting-edge computational approaches and data resources for predicting and analyzing RNA editing sites. Lastly, we cover the recent advancement in site-directed ADAR editing tool development. This review presents an up-to-date overview of ADAR-mediated RNA editing, how site-specific RNA editing could potentially impact disease pathology, and how they could be harnessed for therapeutic applications.

The Tryptophan and Kynurenine Pathway Involved in the Development of Immune-Related Diseases.

The tryptophan and kynurenine pathway is well-known to play an important role in nervous, endocrine, and immune systems, as well as in the development of inflammatory diseases. It has been documented that some kynurenine metabolites are considered to have anti-oxidative, anti-inflammatory, and/or neuroprotective properties. Importantly, many of these kynurenine metabolites may possess immune-regulatory properties that could alleviate the inflammation response. The abnormal activation of the tryptophan and kynurenine pathway might be involved in the pathophysiological process of various immune-related diseases, such as inflammatory bowel disease, cardiovascular disease, osteoporosis, and/or polycystic ovary syndrome. Interestingly, kynurenine metabolites may be involved in the brain memory system and/or intricate immunity via the modulation of glial function. In the further deliberation of this concept with engram, the roles of gut microbiota could lead to the development of remarkable treatments for the prevention of and/or the therapeutics for various intractable immune-related diseases.

Advanced Glycation End-Products Acting as Immunomodulators for Chronic Inflammation, Inflammaging and Carcinogenesis in Patients with Diabetes and Immune-Related Diseases.

Increased production of advanced glycation end products (AGEs) among reducing sugars (glucose, fructose, galactose, or ribose) and amino acids/proteins via non-enzymatic Maillard reaction can be found in lifestyle-related disease (LSRD), metabolic syndrome (MetS), and obesity and immune-related diseases. Increased serum levels of AGEs may induce aging, diabetic complications, cardiovascular diseases (CVD), neurodegenerative diseases (NDD), cancer, and inflamm-aging (inflammation with immunosenescence). The Maillard reaction can also occur among reducing sugars and lipoproteins or DNAs to alter their structure and induce immunogenicity/genotoxicity for carcinogenesis. AGEs, as danger-associated molecular pattern molecules (DAMPs), operate via binding to receptor for AGE (RAGE) or other scavenger receptors on cell surface to activate PI3K-Akt-, P38-MAPK-, ERK1/2-JNK-, and MyD88-induced NF-κB signaling pathways to mediate various pathological effects. Recently, the concept of "inflamm-aging" became more defined, and we have unveiled some interesting findings in relation to it. The purpose of the present review is to dissect the potential molecular basis of inflamm-aging in patients with diabetes and immune-mediated diseases caused by different AGEs.

Role of chemokine-like factor 1 as an inflammatory marker in diseases.

Immunoinflammatory mechanisms have been incrementally found to be involved in the pathogenesis of multiple diseases, with chemokines being the main drivers of immune cell infiltration in the inflammatory response. Chemokine-like factor 1 (CKLF1), a novel chemokine, is highly expressed in the human peripheral blood leukocytes and exerts broad-spectrum chemotactic and pro-proliferative effects by activating multiple downstream signaling pathways upon binding to its functional receptors. Furthermore, the relationship between CKLF1 overexpression and various systemic diseases has been demonstrated in both in vivo and in vitro experiments. In this context, it is promising that clarifying the downstream mechanism of CKLF1 and identifying its upstream regulatory sites can yield new strategies for targeted therapeutics of immunoinflammatory diseases.

Langerin-expressing dendritic cells in pulmonary immune-related diseases.

Dendritic cells (DCs) are "frontline" immune cells dedicated to antigen presentation. They serve as an important bridge connecting innate and adaptive immunity, and express various receptors for antigen capture. DCs are divided into various subclasses according to their differential expression of cell surface receptors and different subclasses of DCs exhibit specific immunological characteristics. Exploring the common features of each sub-category has became the focus of many studies. There are certain amounts of DCs expressing langerin in airways and peripheral lungs while the precise mechanism by which langerin+ DCs drive pulmonary disease is unclear. Langerin-expressing DCs can be further subdivided into numerous subtypes based on the co-expressed receptors, but here, we identify commonalities across these subtypes that point to the major role of langerin. Better understanding is required to clarify key disease pathways and determine potential new therapeutic approaches.

The pivotal roles of neddylation pathway in immunoregulation.

INTRODUCTION: Protein neddylation, one of the most important posttranslational modifications that tagging neuronal precursor cell-expressed developmentally downregulated protein 8 onto substrate proteins, plays fundamental roles in the process of many cellular functions. A number of studies have demonstrated the critical roles of neddylation modification in multiple pathophysiological processes, but its regulatory role in the immune system has only been finitely unveiled. METHODS: In this review, the latest advances in the field of neddylation modification in regulating the immune responses are succinctly discussed. RESULTS: Neddylation modification acts as a crucial modulator of innate immune cells (neutrophils, macrophages, and dendritic cells) and lymphocytes. Dysregulation of neddylation alters characteristics and functions of those cells due to abnormal degradation of key signaling molecules involved in immunoregulation. Furthermore, the ectopic immune responses caused by the abnormal neddylation play pivotal roles in a variety of immune-related diseases, such as infection, inflammation, and cancer. CONCLUSIONS: The pivotal roles of neddylation pathway in immunoregulation are attracted more and more attention, which may provide new insights into the pathogenesis of a variety of immune-related diseases and help to indicate new therapeutic targets and potential treatment strategies.

Current Research of Trichinellosis in China.

Trichinellosis, caused by Trichinella, is an emerging or re-emerging zoonotic parasitic disease, which is distributed worldwide with major socio-economic importance in some developing countries. In particular, it has been calculated that more than 40 million people are at risk of Trichinella infection in China. This review summarizes the current information on the epidemiology, laboratory diagnosis and vaccines of trichinellosis in China. Moreover, study of the treatment potential of using Trichinella for immune-related diseases and cancer, as well as the transcription and post-transcription modification of Trichinella were also collected, providing viewpoints for future investigations. Current advances in research will help us to develop new strategies for the prevention and control of trichinellosis and may potentially yield biological agents for treating other diseases.

Association between CD40 rs1883832 and immune-related diseases susceptibility: A meta-analysis.

BACKGROUND/OBJECTIVE: It has been reported that CD40 rs1883832 might be associated with immune-related diseases susceptibility. Owing to mixed and inconclusive results, we conducted a meta-analysis of case-control studies to summarize and clarify this association. METHODS/MAIN RESULTS: A systematic search of studies on the association between CD40 rs1883832 and immune-related diseases susceptibility was conducted in databases. Odds ratios and 95% confidence intervals were used to pool the effect size. 40 articles were included in our meta-analysis. CONCLUSIONS: CD40 rs1883832 is associated with decreased risk of Graves' disease, especially in Asian; CD40 rs1883832 is associated with increased risk of multiple sclerosis; CD40 -1C>T (rs1883832) is not associated with the susceptibility of Hashimoto's thyroiditis, systemic sclerosis or Asthma; there is insufficient data to fully confirm the association between CD40 rs1883832 and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Behçet's disease (BD), myasthenia gravis (MG), Crohn's disease (CD), ulcerative colitis (UC), Sarcoidosis, Fuch uveitis syndrome (FUS), Vogt-Koyanagi-Harada syndrome (VKH), Kawasaki disease (KD), giant cell arteritis (GCA) or Immune thrombocytopenia (ITP).

FCRL3 gene polymorphisms confer risk for sudden sensorineural hearing loss in a Chinese Han Population.

Fc receptor-like 3 (FCRL3) has recently been associated with susceptibility to several immune-related diseases. In this study, we evaluated the potential association of FCRL3 polymorphisms with sudden sensorineural hearing loss (SSNHL) in a Chinese Han population. Five single-nucleotide polymorphisms (SNPs) in FCRL3-rs945635, rs3761959, rs7522061, rs10489678, and rs7528684-were genotyped in 630 patients with SSNHL and 600 healthy controls by using a PCR-restriction fragment length polymorphism assay. The allele, genotype, and haplotype frequencies in the patients and the controls were compared using a χ(2) test. Moreover, we performed haplotype analysis by using the online software platform SHEsis. The results revealed a significant association between three SNPs-rs7528684, rs3761959, and rs7522061-and SSNHL in the studied Chinese Han population. Furthermore, the AGT and GAC haplotypes were associated with a significantly higher prevalence of SSNHL than were the GAT, GGC and GGT haplotypes. However, no significant differences were detected in either the genotype or allele frequencies of the other two SNPs, rs945635 and rs10489678, between the SSNHL and control groups. Overall, this study has identified an association between FCRL3 polymorphisms and increased risk of SSNHL in a Chinese Han population.

Association between macrophage migration inhibitory factor (MIF) -173G/C gene polymorphism and susceptibility to immune-related diseases in Chinese Han population: a meta-analysis / 中华微生物学和免疫学杂志

Objective@#To investigate the association between macrophage migration inhibitory factor (MIF) -173G/C gene polymorphism and the susceptibility to immune-related diseases in Chinese Han population.@*Methods@#Databases of Wanfang, China National Knowledge Infrastructure (CNKI), PubMed, Excerpta Medica dataBASE (EMbase) and Web of Science (WOS) were comprehensively searched for pertinent articles published in Chinese and English. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used as effect size measures. Publication bias was examined by Brgge′s funnel plots and Egger′s test. Revman 5.3 and STATA 12.0 software were used for statistical analysis.@*Results@#Nine articles were included in this meta-analysis and the studied immune-related diseases included UC (ulcerative colitis), CD (Crohn′s disease), RA (rheumatoid arthritis), PS (psoriasis), asthma, BD (Behçet′s disease), VKH (Vogt-Koyanagi-Harada syndrome), AOSD (adult-onset Still′s disease) and AD (atopic dermatitis). The overall result of the meta-analysis showed that the MIF 173G/C gene polymorphism could increase the susceptibility to immune-related diseases in Chinese Han people (recessive genetic model: OR=1.92, 95%CI: 1.44-2.58; dominant genetic model: OR=1.44, 95%CI: 1.28-1.61; allele model: OR=1.34, 95%CI: 1.22-1.34; homozygote model: OR=1.98, 95%CI: 1.51-2.60; heterozygote model: OR=1.24, 95%CI: 1.11-1.40; all P<0.01). In addition, a subgroup analysis of the North and South of China showed that except for the heterozygote model in the North group, the recessive model (OR=2.03, 95%CI: 1.24-3.31), dominant genetic model (OR=1.51, 95%CI: 1.24-1.83), allele model (OR=1.37, 95%CI: 1.22-1.54) and homozygote model (OR=2.08, 95%CI: 1.31-2.30) all had statistical significance. All of the five models in the South group showed statistical significance (recessive model: OR=1.88, 95%CI: 1.31-2.69; dominant genetic model: OR=1.40, 95%CI: 1.22-1.61; allele model: OR=1.29, 95%CI: 1.10-1.52; homozygote model: OR=1.93, 95%CI: 1.38-2.71; heterozygote model: OR=1.19, 95%CI: 1.08-1.31; all P<0.05).@*Conclusion@#The polymorphism of MIF -173G/C gene may be a susceptible gene to immune-related diseases in Chinese Han people.