Current Immunology Reviews (Discontinued) - Volume 14, Issue 1, 2018

Background: The Unfolded Protein Response (UPR) is a well conserved mechanism that mammalian cells use to cope with stress and infections. This mechanism is exquisitely regulated at several levels, including post-transcriptional modifications by microRNAs. These small non-coding RNAs are mainly involved in the degradation of mRNA, thereby blocking protein translation. The finely balanced interplay between the UPR and microRNAs is altered in several disorders, contributing to both disease aetiology and pathology. Methods: We review and explore alterations in the UPR and microRNAs in several inflammatory conditions, including bone, lung, and neurodegenerative diseases. We also evaluate the impact of these alterations on the disruption of cellular homeostasis and suggest possible therapeutic options to restore this balance. Results: Several components of the UPR, including IRE1, ATF6, and PERK, are clearly dysregulated in inflammatory bone, lung, and neurodegenerative diseases, contributing to the inflammatory process in these disorders. XBP1s, which is downstream of IRE1, is shown to be dysregulated in several diseases, and significantly contributes to the inflammatory process. MicroRNAs show unique dysregulated signatures in each individual tissue and disorder, suggesting that these small transcripts may regulate different pathways in a cell-dependent manner. Finally, there are functional connections between these dysregulated microRNAs and the UPR, which may underlie important pathological aspects of these disorders. Conclusion: It is evident that microRNAs regulate several components of the UPR and that these small non-coding RNAs, or other molecules that restore the UPR balance, may represent possible therapeutic options to normalise intracellular homeostasis.

Background: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system, characterized by progressive neurological dysfunction and recurrent multifocal exacerbations of neurological signs and symptoms. Infiltration of autoreactive lymphocytes and macrophages into the brain parenchyma produces excessive release of reactive oxygen species (ROS), reactive nitrogen species (RNS) and pro-inflammatory cytokines, which creates an elevated oxidative stress in multiple sclerosis patients. Method: A literature search was performed using the PubMed database from 2000 to July 2017. Results: Oxidative stress severely damages the oligodendrocytes and contributes to axonal degeneration. Recent clinical studies suggest the beneficial role of n-3 polyunsaturated fatty acids (PUFAs) and melatonin dietary supplementation in MS pathogenesis. Particularly, dietary supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) significantly reduces serum markers of oxidative stress and inflammation in relapsing-remitting multiple sclerosis. Melatonin also shows beneficial immunomodulatory and antioxidant effects on MS. Conclusion: Dietary intake of PUFAs and melatonin could also be considered as adjuvant treatments for that clinical course of relapsing-recurrent multiple sclerosis. Further studies focusing on the role of endocannabinoids derived from PUFA´s in MS are needed.

Background: Sjögren's Syndrome (SS) is the second most common autoimmune rheumatic disease after rheumatoid arthritis and affects approximately 1 to 3% of the population. Most patients affected by Sjogren's syndrome manifest otorhinolaryngological involvement, such as glandular, ocular, oral, otological, pharyngeal, laryngeal and sinonasal symptoms. Objective: The aim of this article is to emphasize the otorhinolaryngological manifestations of SS. Since otorhinolaryngologists are often the first practitioners to detect the symptoms, a complete and careful ENT examination should be performed in all the patients suspected to have this syndrome. Conclusion: To date, there is no straight forward and reliable diagnostic test for Sjögren's syndrome. Its diagnosis can be difficult because the signs and symptoms vary widely and sometimes are similar to those caused by other diseases. Hence, it is important to identify conditions with similar patterns in order to make a correct diagnosis, begin the appropriate therapy, determine a proper follow-up and ensure a good quality of life.

Background: Chikungunya infections are a major concern because of their persistent recurrence in the last few decades. Chikungunya virus (CHIKV) is a mosquito borne alpha virus that causes an acute febrile illness accompanied by body rashes, myalgia and polyarthralgia; which may persists for years. Chikungunya fever, affect millions of people in Africa, Asia, including the Indian subcontinent and lately in several regions of the Americas. No specific antivirals and vaccines are currently available to treat or prevent the disease. Methods: Understanding the mechanisms of host immune responses to CHIKV and the immunopathology of the disease is essential for the development of vaccines and diagnostics. Many studies have demonstrated the role of the immune response in the immunopathology of the disease and in the host's incapability to clear the virus efficiently. In this review the excellence of the referenced papers were evaluated using standard tools. Results: Total seventy-four papers were included in the review. Majority of them were highlighted the importance of understanding the immunopathology of virus, contributing factor and control measures of the epidemics. Nineteen papers were provided the current occurrence and re-emergence of the disease. The diagnostic importance (sensitivity and specificity) of developed diagnostics for the early detection were also provided in eight papers. Conclusion: In the current review we highlighted the importance of conceptual mechanism of the host immune responses to CHIKV and the immunopathology of this alpha virus. The presented review provides an update on the infection, its vector, and the disease transmission, research development, and administration for avoidance of Chikungunya disease.

Background: Vitamin D has mainly been described in the literature beyond its skeletal functions, including an influence on the immune responses against infections. Observational and interventional studies have represented evidence that Vitamin D deficiency may cause increased risk of seasonal influenza and pulmonary tract infection. Methods: A structured search of EMBASE, Medline, and Web of Science databases was fulfilled to extract all eligible articles published prior to September 2017. Results: In this review, our goal is to define the possible mechanisms that link influenza-mediated immune responses to Vitamin D. Herein, we first briefly describe the role of Vitamin D in the immune responses and then elucidate three immunological processes that connect Vitamin D to influenza infection. Finally, we describe randomized controlled trials and observational studies exploring the effect of Vitamin D supplementation on seasonal influenza infections and vaccinations. Conclusion: Our literature review suggests that treatment of influenza-infected individuals with Vitamin D supplements or cathelicidin-derived agents may provide appreciable protection against natural influenza infection. Moreover, Vitamin D given at appropriate doses may facilitate protection against seasonal flu.

Background: Recurrent Miscarriage (RM) is one of the most frustrating clinical situations wherein most of the cases, neither the engaged obstetrician nor suffering couples know the exact etiology and cause of the disease. About 10-15% of women with RM diagnosed with antiphospholipid syndrome (APS) are characterized by the marked presence of antiphospholipid antibodies (aPLa). There are several scientific reports available on the association between APS and RM; however, scanty data available about the beneficial role of coenzyme Q10 (CoQ10) in APS and APS mediated RM. In the present attempt, we tried to gather information to explain the possible associations between the role of CoQ10 in RM and APS. Methods: We collected peer-reviewed literature using keywords; antiphospholipid syndrome, CoQ10, endothelial dysfunction, oxidative stress and recurrent miscarriage in online electronic databases, such as Web of Science, Science Direct, Google Scholar, PubMed and Medline. The qualitative analysis of content was done by summarizing interventions and findings of included studies, on the basis of which a conceptual framework was prepared for this narrative review. Results: The beneficial role of CoQ10 in diverse pathological conditions has been summarized and the evidence suggests that CoQ10 being a potent antioxidant helps in the amelioration of free radicalmediated aPLa production, endothelial damage and mitochondrial dysfunction. The supplementation of CoQ10 overcomes the immune dysregulation in idiopathic RM and APS; thus could be a possible therapeutic adjunct in such diseases. Conclusion: Based on this review, further comprehensive studies may be conducted to illuminate the beneficial therapeutic effects of supplementing CoQ10 on possible modifiable pathways involved in the progression of RM and APS.

Background: Epidemiological studies have shown the role of high dietary fat intake as a risk factor for Neuropsychiatric Disorders (NPDs). However, the exact mechanism of this phenomenon is unknown. Methods: An electronic search was performed using Scopus, PubMed and Google Scholar regarding the association of high fat intake and inflammatory reactions and their roles in the etiopathogenesis of NPDs. Results: The results indicate that high fat intake is involved in the development of severe inflammatory reactions. Inflammation is also involved in the pathophysiology of NPDs. Therefore, it is suggested that high fat intake might be involved in the development of NPDs through induction of inflammatory reactions. Conclusion: It is suggested that reducing fat intake might decline the risk of NPDs.

Systemic lupus erythematosus (SLE) is an autoimmune disease whose etiology and pathogenesis are incompletely understood. Over the past 50-60 years, there has been a rise of more than ten-fold in the annual incidence of SLE in industrialized Western countries. Although it is believed that the etiology of SLE is multifactorial, including genetic, hormonal and environmental triggers, the molecular mechanisms underlying this systemic autoimmune response remain largely unknown. Clinical and epidemiological studies have revealed that SLE is rarely observed in rural tropical areas of Africa and Asia, where parasitic infections are prevalent. Indeed, tropical infections, particularly malaria, have a mysterious relation with SLE. In this review, we will focus on this relationship between infections and lupus as a prototypic autoimmune disease.