Search

Th17 cells remain one of the most important subsets of T cells in numerous autoimmune and chronic inflammatory diseases. Posttranscriptional regulation (PTR), especially mRNA stability, has recently emerged as an important mechanism that controls the fate of Th17 cells. This review summarizes the current knowledge on RNA-binding proteins (RBPs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that induce mRNA stability changes and their roles in mediating the differentiation, proliferation, function, and migration of Th17 cells. In addition, we summarize the role of RNA modifications and nonsense-mediated mRNA decay (NMD) in Th17 cells. Ongoing research will help to identify practical applications for the regulation of mRNA stability and provide potential targets to prevent and treat Th17-related autoimmune diseases.

The most recently recognized types of immune cells, the innate lymphoid cells (ILCs), have been sub-divided according to respective distinct expression profiles of regulatory factors or/and cytokines. ILCs have also been shown to participate in a variety of beneficial immune responses, including participation in attack against pathogens and mediation of the pre-inflammatory and inflammatory responses through their production of pro-inflammatory cytokines. As such, while the ILCs exert protective effects they may also become detrimental upon dysregulation. Indeed, recent studies of the ILCs have revealed a strong association with the advent and pathogenesis of several common autoimmune diseases, including psoriasis, inflammatory bowel disease (IBD) and multiple sclerosis (MS). Though the ILCs belong to lineage negative cells that are distinctive from the Th cells, the profiles of secreted cytokines from the ILCs overlap with those of the corresponding Th subsets. Nevertheless, considering that the ILCs belong to the innate immune system and the Th cells belong to the adaptive immune system, it is expected that the ILCs should function at the early stage of diseases and the Th cells should exert predominant effects at the late stage of diseases. Therefore, it is intriguing to consider targeting of ILCs for therapy by targeting the corresponding cytokines at the early stage of diseases, with the late stage cytokine targeting mainly influencing the Th cells' function. Here, we review the knowledge to date on the roles of ILCs in various autoimmune diseases and discuss their potential as new therapeutic targets., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease of unknown etiology. The epigenetic regulation of N6-methyladenosine (m6A) modification in immunity is emerging. However, few studies have focused on SLE and m6A immune regulation. In this study, we aimed to explore a potential integrated model of m6A immunity in SLE. The models were constructed based on RNA-seq data of SLE. A consensus clustering algorithm was applied to reveal the m6A-immune signature using principal component analysis (PCA). Univariate and multivariate Cox regression analyses and Kaplan–Meier analysis were used to evaluate diagnostic differences between groups. The effects of m6A immune-related characteristics were investigated, including risk evaluation of m6A immune phenotype-related characteristics, immune cell infiltration profiles, diagnostic value, and enrichment pathways. CIBERSORT, ESTIMATE, and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate the relative immune cell infiltrations (ICIs) of the samples. Conventional bioinformatics methods were used to identify key m6A regulators, pathways, gene modules, and the coexpression network of SLE. In summary, our study revealed that IGFBP3 (as a key m6A regulator) and two pivotal immune genes (CD14 and IDO1) may aid in the diagnosis and treatment of SLE. The potential integrated models of m6A immunity that we developed could guide clinical management and may contribute to the development of personalized immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) represent a newly identified class of non-coding RNAs that have been shown to be involved in several diseases, including autoimmune diseases. Two studies have revealed the aberrant circRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA) by microarrays. However, due to the intrinsic defects of microarrays, such as their inability to detect unidentified circRNAs, we examined the circRNA expression profiles in the PBMCs from four RA patients and three healthy controls by RNA sequencing (RNA-seq) and further explored the value of circRNAs in diagnosing RA. The results showed 71 markedly dysregulated circRNAs, including 41 upregulated and 30 downregulated circRNAs; these data included several previously unidentified candidate circRNAs. Gene Ontology and pathway annotation revealed that the most altered pathways and genes were associated with inflammation and transcriptional activity, such as the TNF pathway. The selected dysregulated circRNAs were verified by qRT-PCR in the PBMCs of 32 RA patients and 20 healthy controls, and the results indicated that hsa_circ_0000396 and hsa_circ_0130438 were downregulated in the RA group versus the healthy group, consistent with the RNA-seq data. The area under the receiver operating characteristic curve indicated the diagnostic value of both circRNAs for RA. Our results identified aberrant dysregulated circRNAs in RA patients, including several identified circRNAs, and the diagnostic value of circRNAs for RA, suggesting the superiority of RNA-seq versus microarrays for screening differentially expressed circRNAs and further strengthening the potential diagnostic value of circRNAs for the diagnosis of RA. [ABSTRACT FROM AUTHOR]

CD4++ T helper (Th) cells act as important regulators of the mammalian adaptive immune response. CD4++ Th cells were originally characterized as either Th1 or Th2 types, based on the cytokines they produce. Over the past two decades, however, we have attained a much more detailed understanding of CD4++ T-cell differentiation, functions, and gene expression profiles, which led to the identification of additional types, such as the Th17 and induced regulatory T cells. Recently, researchers have characterized yet another novel and distinct population that exists among these immune-modulatory cells. The ''Th9'' cells were first identified as a Th2 subpopulation that produced exceptionally large quantities of the Th2-specific cytokine interleukin 9. However, experimental analysis revealed that Th9 cells had divergent regulatory capabilities and were critically involved in different immune processes. In particular, we now know that Th9 acts as a major contributor to the onset and progression of allergies, especially asthma. Here, we will review the heterogeneity and biology of CD4++ Th cells and summarize the characteristics known to date of interleukin 9 and Th9 cells to build a framework for better understanding of their roles in disease processes, especially in allergy-induced asthma. [ABSTRACT FROM AUTHOR]