NAFLD patients have decreased serum 25(OH)D concentrations, suggesting that vitamin D may play a role in the development of NAFLD. The directionality of this association cannot be determined from cross-sectional studies. Demonstration of a causal role of hypovitaminosis D in NAFLD development in future studies could have important therapeutic implications.
Dendritic cell (DC) activation by nucleic acid-containing IgG complexes is implicated in systemic lupus erythematosus (SLE) pathogenesis. However, it has been difficult to definitively examine the receptors and signaling pathways by which this activation is mediated. Because mouse FcγRs recognize human IgG, we hypothesized that IgG from lupus patients might stimulate mouse DCs, thereby facilitating this analysis. In this study, we show that sera and purified IgG from lupus patients activate mouse DCs to produce IFN-α, IFN-β, and IL-6 and up-regulate costimulatory molecules in a FcγR-dependent manner. This activation is only seen in sera with reactivity against ribonucleoproteins and is completely dependent on TLR7 and the presence of RNA. As anticipated, IFN regulatory factor (IRF)7 is required for IFN-α and IFN-β production. Unexpectedly, however, IRF5 plays a critical role in IFN-α and IFN-β production induced not only by RNA-containing immune complexes but also by conventional TLR7 and TLR9 ligands. Moreover, DC production of IL-6 induced by these stimuli is dependent on a functional type I IFNR, indicating the need for a type I IFN-dependent feedback loop in the production of inflammatory cytokines. This system may also prove useful for the study of receptors and signaling pathways used by immune complexes in other human diseases.
Background and Aims
Hepatitis C virus (HCV)‐viremic organs are underutilized, and there is limited real‐world experience on the transplantation of HCV‐viremic solid organs into recipients who are HCV negative.
Approach and Results
Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV‐viremic organs. All recipients were HCV nucleic acid test and anti‐HCV antibody negative at the time of transplant and received an HCV‐viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct‐acting antiviral (DAA) therapy (SVR12). Seventy‐seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty‐four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty‐one achieved SVR12, 10 had undetectable viral loads but are not eligible for SVR12, and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver‐kidney transplant. Three patients achieved SVR12, 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart‐kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment.
Conclusions
Limited data exist on the transplantation of HCV‐viremic organs into recipients who are HCV negative. Our study is the largest to describe a real‐world experience of the transplantation of HCV‐viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV‐viremic grafts in the DAA era appears to be efficacious and well tolerated.
A significant degree of fibrosis and muscularis mucosae thickening should be considered as common complications of chronic progressive ulcerative colitis. These features may have clinical consequences such as motility abnormalities and increased wall stiffness.
Background: RNA interference (RNAi) is a useful tool to know the function of a gene in a cell under any kind of stress. Results: RNAi-mediated knockdown of genes in dendritic cells identified unreported genes and pathways that regulate its various functions during Mycobacterium tuberculosis infection.
Conclusion:The identified genes could be potential targets in drug and vaccine designing. Significance: Understanding the role of host factors that regulate priming of immune responses is crucial to study hostpathogen interactions.
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