Molecular immunology
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Molecular immunology · Nov 2015
Review Historical ArticleMembranous nephropathy: A fairy tale for immunopathologists, nephrologists and patients.
This article reviews the considerable progress which has been made in the recent years in the understanding of the pathophysiology of membranous nephropathy, a model of organ-specific auto-immune disease. It shows how experimental models developed more than 30 years ago have led to the identification of several human antigens including neutral endopeptidase in the neonate, phospholipase A2 receptor, and thrombospondin 1 domain 7A in the adult, and cationic bovine serum albumin in children. Thanks to a successful GWAS performed in European Caucasians, the genetics of the disease begins to be understood. ⋯ It is remarkable that in this disease, the experimental models predicted the pathophysiology of the human glomerulopathy. The stories that we will tell in this article are aimed at young clinical investigators who are sometimes reluctant to embark on research projects. We hope that they will convince them that bedside research performed with intellectual curiosity and a bit of chance can lead to significant progress in clinical medicine.
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Molecular immunology · Sep 2015
ReviewParoxysmal nocturnal hemoglobinuria (PNH) and primary p.Cys89Tyr mutation in CD59: Differences and similarities.
CD59 encodes a 77 amino acid glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that inhibits the final step of membrane attack complex (MAC) formation. CD59 deficiency is a common finding in adult patients with paroxysmal nocturnal hemoglobinuria (PNH). In this condition, there is a clonal expansion of hematopoietic stem cells that have acquired a mutation in the PIGA gene (phosphatidylinositol glycan anchor biosynthesis, class A). ⋯ Cys89Tyr with resulting failure of proper localization of the CD59 protein to the cell surface. The Cys89Tyr mutation in CD59 was clinically manifested in infancy, and associated with chronic hemolysis and relapsing peripheral demyelinating disease resembling recurrent Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP). In this review we describe differences and similarities in the pathogenesis and clinical manifestations of PNH and primary CD59 Cys89Tyr mutation with the aim of tracking the contribution of CD59 deficiency to the pathophysiology and perhaps deepening our understanding of both diseases.
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Molecular immunology · Aug 2015
Mechanisms that lead to the regulation of NLRP3 inflammasome expression and activation in human dental pulp fibroblasts.
The NLRP3 inflammasome plays an important role in the cellular defense against invading pathogens and is reported to be expressed in human dental pulp fibroblasts (HDPFs). However, the role of the NLRP3 inflammasome in HDPFs during pulpal infection and inflammation remains unclear. ⋯ Our results demonstrated that the NLRP3 inflammasome in HDPFs is crucial for IL-1β secretion in response to LPS plus ATP. LPS engaged the TLR4/MyD88/NF-κB pathway to enhance NLRP3 and pro-IL-1β expression in HDPFs. ATP promoted the generation of ROS and activated the NLRP3 inflammasome in a ROS-dependent manner.
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Molecular immunology · Aug 2015
Enhanced and durable protective immune responses induced by a cocktail of recombinant BCG strains expressing antigens of multistage of Mycobacterium tuberculosis.
Although Bacillus Calmette-Guérin (BCG) vaccine confers protection from Mycobacterium tuberculosis infection in children, its immune protection gradually wanes over time, and consequently leads to an inability to prevent the reactivation of latent infection of M. tuberculosis. Therefore, improving BCG for better control of tuberculosis (TB) is urgently needed. We thus hypothesized that recombinant BCG overexpressing immunodominant antigens expressed at different growth stages of M. tuberculosis could provide a more comprehensive protection against primary and latent M. tuberculosis infection. ⋯ Our results showed that ABX was able to induce a stronger immune protection than individual rBCGs or BCG against primary TB infection in C57BL/6 mice. Mechanistically, the immune protection was attributed to stronger antigen-specific CD4(+) Th1 responses, higher numbers of IFN-γ(+) CD4(+) TEM and IL-2(+) CD8(+) TCM cells elicited by ABX. These findings thus provide a novel strategy for the improvement of BCG efficacy and potentially a promising prophylactic TB vaccine candidate, warranting further investigation.
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Molecular immunology · Aug 2015
Soluble monosodium urate, but not its crystal, induces toll like receptor 4-dependent immune activation in renal mesangial cells.
Uric acid has emerged as a novel and potential modifiable risk factor for the incidence and progression of kidney diseases, however, the deteriorate effect of uric acid on renal mesangial cells remains unclear. The present study is to examine the immune activation of soluble and crystal forms of uric acid in human mesangial cells. ⋯ Our results suggested that soluble MSU, but not MSU crystals, induce NLRP3, IL-1β, HLA-DR and CD40 upregulation in a TLR4-dependent manner. These findings indicate that soluble MSU may play a pathological role in hyperuricemia induced renal mesangial injury.