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Exosomes are spherical lipid bilayer vesicles composed of lipids, proteins and nucleic acids that deliver signaling molecules through a vesicular transport system to regulate the function and morphology of target cells, thereby involving in a variety of biological processes, such as cell apoptosis or proliferation, and cytokine production. In the past decades, there are emerging evidence that exosomes play pivotal roles in the pathological mechanisms of several autoimmune diseases (ADs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), Sjogren's syndrome (SS), multiple sclerosis (MS), inflammatory bowel disease (IBD). systemic sclerosis (SSc), etc. Several publications have shown that exosomes are involved in the pathogenesis of ADs mainly through intercellular communication and by influencing the response of immune cells. The level of exosomes and the expression of nucleic acids can reflect the degree of disease progression and are excellent biomarkers for ADs. In addition, exosomes have the potential to be used as drug carriers thanks to their biocompatibility and stability. In this review, we briefly summarized the current researches regarding the biological functions of exosomes in ADs, and provided an insight into the potential of exosomes as biomarkers and therapeutic delivery for these diseases.

Autoimmune diseases (ADs) are a broad range of disorders which are characterized by long-term inflammation and tissue damage arising from an immune response against one's own tissues. It is now widely accepted that the causes of ADs include environmental factors, genetic susceptibility and immune dysregulation. However, the exact etiology of ADs has not been fully elucidated to date. Because observational studies are plagued by confounding factors and reverse causality, no firm conclusions can be drawn about the etiology of ADs. Over the years, Mendelian randomization (MR) analysis has come into focus, offering unique perspectives and insights into the etiology of ADs and promising the discovery of potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly dispensed during meiosis, usually irrespective of environmental or lifestyle factors) is used instead of modifiable exposure to explore the link between exposure factors and disease or other outcomes. Therefore, MR analysis can provide a valuable method for exploring the causal relationship between different risk factors and ADs when its inherent assumptions and limitations are fully considered. This review summarized the recent findings of MR in major ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM), focused on the effects of different risk factors on ADs risks. In addition, we also discussed the opportunities and challenges of MR methods in ADs research.

Autoimmune diseases (ADs) are a broad spectrum of disorders featured by the body's immune responses being directed against its own tissues, resulting in prolonged inflammation and subsequent tissue damage. Recently, the exposure to ambient air pollution has been implicated in the occurrence and development of ADs. Mechanisms linking air pollution exposures and ADs mainly include systemic inflammation, increased oxidative stress, epigenetic modifications induced by exposures and immune response caused by airway damage. The lung may be an autoimmunity initiation site in autoimmune diseases (ADs). Air pollutants can bind to the Aryl hydrocarbon receptor (AHR) to regulate Th17 and Treg cells. Oxidative stress and inducible bronchus associated lymphoid tissue caused by the pollutants can influence T, B cells, resulting in the production of proinflammatory cytokines. These cytokines stimulate B cell and dendritic cells, resulting in a lot of antibodies and self-reactive T lymphocytes. Moreover, air pollutants may induce epigenetic changes to contribute to ADs. In this review, we will concern the associations between air pollution and immune-inflammatory responses, as well as mechanisms linking air pollution exposure and autoimmunity. In addition, we focus on the potential roles of air pollution in major autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM).

Pentraxin 3 (PTX3) is a prototypic humoral soluble pattern recognition molecule that exerts a pivotal role in innate immune response and inflammation, as well as in tissue damage and remodeling. Recently, emerging evidence has revealed that PTX3 is involved in the occurrence and development of various autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), systemic sclerosis (SSc), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis, etc. In this review, we have succinctly summarized the complex immunological functions of PTX3 and mostly focused on recent findings of the pleiotropic activities played by PTX3 in the pathogenesis of autoimmune diseases, aiming at hopefully offering possible future therapeutic alternatives.

NLRP3, a member of nucleotide-binding domain-(NOD) like receptor family, can be found in large varieties of immune and non-immune cells. Upon activation, the NLRP3, apoptosis-associated speck-like protein (ASC) and pro-caspase-1 would assemble into a multimeric protein, called the NLRP3 inflammasome. Then the inflammasome promotes inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. Previous studies have indicated the importance of NLRP3 in regulating innate immunity. Recently, numerous studies have revealed their significance in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) and inflammatory bowel disease (IBD). In this review, we will briefly discuss the biological features of NLRP3 and summarize the recent progression of the involvement of NLRP3 in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which immune regulation is disrupted and characterized by intense inflammation and damage to multiple organs or systems. Rheumatoid arthritis (RA) is another systemic autoimmune disease characterized by chronic synovial joint inflammation that leads to disability and poor quality of life. Although the etiologies and pathogenesis of SLE and RA are not fully understood, it is generally accepted that they are both caused by interactions between genetic and environmental factors. In recent years, emerging studies have demonstrated the potential role of seasonality in the development and disease activity of variety of autoimmune diseases [[1], [2], [3]].

Circadian rhythm is a natural, endogenous process whose physiological functions are controlled by a set of clock genes. Disturbance of the clock genes have detrimental effects on both innate and adaptive immunity, which significantly enhance pro-inflammatory responses and susceptibility to autoimmune diseases via strictly controlling the individual cellular components of the immune system that initiate and perpetuate the inflammation pathways. Autoimmune diseases, especially rheumatoid arthritis (RA), often exhibit substantial circadian oscillations, and circadian rhythm is involved in the onset and progression of autoimmune diseases. Mounting evidence indicate that the synthetic ligands of circadian clock genes have the property of reducing the susceptibility and clinical severity of subjects. This review supplies an overview of the roles of circadian clock genes in the pathology of autoimmune diseases, including BMAL1, CLOCK, PER, CRY, REV-ERBα, and ROR. Furthermore, summarized some circadian clock genes as candidate genes for autoimmune diseases and current advancement on therapy of autoimmune diseases with synthetic ligands of circadian clock genes. The existing body of knowledge demonstrates that circadian clock genes are inextricably linked to autoimmune diseases. Future research should pay attention to improve the quality of life of patients with autoimmune diseases and reduce the effects of drug preparation on the normal circadian rhythms.

P2X7 receptor (P2X7R), a distinct ligand-gated ion channel, is a member of purinergic type 2 receptor family with ubiquitous expression in human body. Previous studies have revealed a pivotal role of P2X7R in innate and adaptive immunity. Once activated, it will meditate some vital cascaded responses including the assembly of nucleotide-binding domain (NOD) like receptor protein 3 (NLRP3) inflammasome, non-classical secretion of IL-1β, modulation of cytokine-independent pathways in inflammation such as P2X7R- transglutaminase-2 (TG2) and P2X7R-cathepsin pathway, activation and regulation of T cells, etc. In fact, above responses have been identified to be involved in the development of autoimmunity, specifically, the NLRP3 inflammasome could promote inflammation in massive autoimmune diseases and TG2, as well as cathepsin may contribute to joint destruction and degeneration in inflammatory arthritis. Recently, numerous evidences further suggested the significance of P2X7R in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), etc. In this review, we will succinctly discuss the biological characteristics and summarize the recent progress of the involvement of P2X7R in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.

Systemic lupus erythematosus (SLE) is associated with increased risk of cardiovascular disease. Carotid intima media thickness (CIMT) and carotid plaques are both frequently used to identify populations at higher cardiovascular risk. A systematic literature search and meta-analysis were performed to evaluate CIMT and carotid plaques difference between SLE patients and normal controls.The literatures comparing markers of cardiovascular risk (CIMT and prevalence of carotid plaques) in SLE and controls were systematically searched in PubMed, EMBASE and Cochrane databases. The overall mean CIMT difference and pooled odds ratio (OR) for the prevalence of carotid plaques between SLE patients and control groups were calculated by fixed-effects or random-effect model analysis. Meta-regression was performed to explore the potential influencing factors. Publication bias was examined by a funnel plot and Egger's test.A total of 80 studies (6085 SLE patients and 4794 controls) were included in the final analysis, 71 studies with data on CIMT (4814 cases and 3773 controls) and 44 studies reporting on the prevalence of carotid plaques (4417 cases and 3528 controls). As compared to controls, SLE patients showed a higher CIMT (WMD: 0.07 mm; 95%CI: 0.06, 0.09; P0.001), and an increased prevalence of carotid plaques (OR: 2.45; 95%CI: 2.02, 2.97; P0.001). Meta-regression models showed that traditional cardiovascular risk factors (age, HDL and triglyceride of SLE patients) and lupus related risk factors (as expressed by duration, ESR, SLEDAI and steroids) had a significant influence on CIMT, steroids and triglyceride had significant influence on the prevalence of carotid plaques.Our findings support the current evidence base for an increased cardiovascular burden in SLE patients and support the use of CIMT and carotid plaques in observational studies in SLE patients. The findings are of importance to design more specific prevention and treatment strategies.

Long noncoding RNA (lncRNA), with size larger than 200 nucleotides, is a new class of noncoding RNA. Emerging evidence has revealed that lncRNAs play a key role in the regulation of immunological functions and autoimmunity. Herein, we review the recent findings of lncRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. In addition, we focus on the involvement of lncRNA regulation in innate and adaptive immune responses, immune cell development, and differential expression of lncRNAs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), multiple sclerosis (MS), autoimmune thyroid disease (AITD), psoriasis, polymyositis/dermatomyositis (PM/DM) and Crohn's disease (CD).

As a member of the IRF family of transcription factors, interferon regulatory factor 4 (IRF4) is expressed in most cell types of the immune system. Recent findings suggest that IRF4 is essential for the development and function of T helper (Th) cell, regulatory T (Treg) cell, B cell, as well as dendritic cell (DC). Since these cells are crucial in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease (Crohn's disease and ulcerative colitis), and type I diabetes, the roles of IRF4 in the initiation and progression of autoimmune diseases can not be neglected. In this review, we summarize recent advances on the pathological roles of IRF4 in autoimmunity and discuss the therapeutic significance of these new findings.

E26 transformation–specific-1 (Ets-1) belongs to the Ets family of transcription factors which share a common 85-amino-acid DNA-binding domain. Ets-1 is essential to regulation of the immune system including immune cell proliferation and differentiation. Past data demonstrated Ets-1 play a role in negative regulation of Th17 cells and B cells differentiation. Recently, association of genetic variation in Ets-1 with susceptibility to systemic lupus erythematosus (SLE) have been independently identified by two Genome-wide association studies (GWAS), and decreased Ets-1 mRNA level in peripheral blood mononuclear cells (PBMCs) of SLE patients has been reported. All these findings suggest that the transcription factor is broadly linked to the pathogenesis of this disease. However, aberrant control of other immune cells and effector molecules illuminated the complexities of Ets-1 biology. In this review article, we will focus on the dual nature of Ets-1 and discuss its regulatory capability. Hopefully the information obtained will lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for SLE.