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Hemophagocytosis causes a consumptive anemia of inflammation
IFN-γ stimulates blood-eating macrophages (hemophagocytes) by acting directly on macrophages to promote phagocytosis and uptake of blood cells.
Perforin is a critical physiologic regulator of T-cell activation.
It is concluded that perforin-dependent cytotoxicity has an immunoregulatory role that is distinguishable from its pathogen clearance function and limits T-cell activation in the physiologic context by suppressing antigen presentation. Expand
Mice with a Selective Impairment of IFN-γ Signaling in Macrophage Lineage Cells Demonstrate the Critical Role of IFN-γ–Activated Macrophages for the Control of Protozoan Parasitic Infections In Vivo
The MIIG mouse formally demonstrates for the first time in vivo, the specific importance of direct, IFN-γ mediated activation of macrophages for controlling infection with multiple protozoan parasites. Expand
Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression.
A model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1 is proposed. Expand
The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
Both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF 5- TNPO3. Expand
Lupus risk variants in the PXK locus alter B-cell receptor internalization
A fine-mapping analysis in a large multi-ancestral study of lupus patients and controls finds that PXK operates on the B-cell antigen receptor (BCR) and influences the rate of BCR internalization, highlighting the regulation of intracellular trafficking as a genetically regulated pathway mediating human autoimmunity. Expand
Editorial: What Caused All These Troubles, Anyway? Epstein‐Barr Virus in Sjögren's Syndrome Reevaluated
Knowing that the host response to Streptococci is responsible for rheumatic fever seems to have contributed to the authors' therapeutic success with this disease and its demise as a public health scourge, despite the many important details that remain unexplained about the relationship of this bacterium to theHost response and the vagaries of disease expression. Expand
A plausibly causal functional lupus-associated risk variant in the STAT1–STAT4 locus
A plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus is presented in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1. Expand
Mechanisms of consumptive anemia of inflammation: Roles for interferon-gamma and hemophagocytosis
Anemia is a widespread and potentially serious clinical problem. Anemia caused by inflammation has been recognized for over 100 years, however the mechanisms behind anemia during acute inflammationExpand