Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed novel genetically lupus-prone (NZB x NZW)F(1)-derived congenic New Zealand mixed (NZM) 2328 lines, which are either Stat4- or Stat6-deficient. Our studies show that the deficiency of Stat4 and Stat6 significantly alters the phenotype of the lupus-like disease in NZM 2328 congenic mice. Specifically, Stat4-deficient NZM mice develop accelerated nephritis and increased mortality in the absence of high levels of autoantibodies including anti-dsDNA Abs, and in the presence of relatively reduced levels of IFN-gamma. In contrast, Stat6-deficient NZM mice display a significant reduction in incidence of kidney disease, with a dramatic increase in survival, despite the presence of high levels of anti-dsDNA Abs. The lack of correlation between levels of these autoantibodies and kidney disease raises the question of the direct cause-effect relationships between the presence of autoantibodies and kidney disease. Furthermore, these results also question the apparent equation of the effect of Stat deficiency with loss of secretion or response to particular cytokines.
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PMID:Pivotal role of Stat4 and Stat6 in the pathogenesis of the lupus-like disease in the New Zealand mixed 2328 mice. 1287 50

Interleukin-4 (IL-4) is a multifunctional cytokine. Although most studies have focused on the B-cell stimulatory and Th2 promoting properties of IL-4 in the development of autoantibodies and autoantibody-mediated diseases, a few reports suggest a T-cell suppressor role for this cytokine in lupus. Since these properties of IL-4 may sometimes result in opposing outcomes, amplifying or inhibitory, on overall B-cell functions, it is not surprising that a few studies have found no role for IL-4 in the development of autoantibodies and lupus. Evidence for a more novel role for IL-4 in the development of lupus nephritis comes from recent studies, which suggests that IL-4 may directly promote extracellular matrix deposition in the glomeruli. Consistent with this idea, blockade of IL-4 by antibody treatment or of its signaling by inactivation of the Stat6 gene ameliorates glomerulosclerosis and delays or even prevents the development of end-stage renal disease, despite the presence of high levels of IgG anti-dsDNA Antibodies. Thus, IL-4 may serve multiple roles in the development of lupus: it may enhance autoantibody production via its direct B-cell effects, protect against autoimmunity via its T-cell suppressor effect, or perpetuate tissue damage via its direct effects on target organs.
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PMID:IL-4 and many roads to lupuslike autoimmunity. 1292 53

To determine the respective role of the IL-12 and IL-4 pathways in the pathogenesis of systemic lupus erythematosus, we bred the Stat4 and Stat6 null alleles onto the lupus-prone mouse B6.TC, which is a congenic derivative of NZM2410. This model is characterized by abnormal splenocyte expansion, distribution and architecture, T cell activation, peripheral B cell development, production of anti-nuclear antibodies, and proliferative glomerulonephritis. STAT4 deficiency normalized the expression of each of these disease markers toward or to C57BL/6 levels. In contrast, STAT6 deficiency impacted splenocyte expansion and architecture, T cell activation, and anti-nuclear autoantibody production, but without any significant effect on B cell development or renal pathology. These results show that the IL-12/STAT4 pathway is involved in multiple disease-associated phenotypes in the B6.TC mouse. In contrast, the IL-4/STAT6 pathway regulates only a subset of disease markers that did not affect renal pathology.
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PMID:STAT4 deficiency reduces autoantibody production and glomerulonephritis in a mouse model of lupus. 1671 41