Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple genetic factors contribute to the clinical variability of spontaneous systemic lupus erythematosus (SLE) but their role in drug-induced SLE remain largely unknown. Hydrocarbon oil-induced SLE depends on mesothelial cell apoptosis and Toll-like receptor (TLR)-7-mediated induction of type I interferons. Hence, we hypothesized that TIR8/SIGIRR, an endogenous TLR inhibitor, prevents oil-induced SLE. Sigirr-deficient dendritic cells expressed higher TLR7 mRNA levels and TLR7 activation resulted in increased IL-12 production in vitro. In vivo, lack of SIGIRR increased surface CD40 expression on spleen CD11c(+) dendritic cells and MX-1, TNF, IL-12, BAFF and BCL-2 mRNA expression 6 months after pristane injection. Spleen cell counts of CD4(-)/CD8(-) 'autoreactive' T cells and B220(+) B cells were also increased in Sigirr(-/-) mice. Serum autoantibody analysis revealed that Sigirr deficiency specifically enhanced the production of rheumatoid factor (from 4 months of age) and anti-snRNP IgG (from 5 months of age), while anti-Smith IgG or anti-dsDNA IgG were independent of the Sigirr genotype. This effect was sufficient to significantly aggravate lupus nephritis in Sigirr-deficient mice. Structure model prediction identified the BB loop of SIGIRR's intracellular TIR domain to interact with TLR7 and MyD88. BB loop deletion was sufficient to completely abrogate SIGIRR's inhibitory effect on TLR7 signalling. Thus, TIR8/SIGIRR protects from hydrocarbon oil-induced lupus by suppressing the TLR7-mediated activation of dendritic cells, via its intracellular BB loop.
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PMID:Lack of SIGIRR/TIR8 aggravates hydrocarbon oil-induced lupus nephritis. 2011 71

In previous studies, we showed that intracerebrally (IC) immunized mice had antigen-specific antibodies (Abs) in cerebrospinal fluid and could survive lethal doses of transneurally spreading viruses. To better understand the mechanisms behind this, immune responses in both the central nervous system (CNS) and lymphoid organs following intracerebral immunization against pseudorabies virus (PRV) were investigated by focusing on antibody secreting cells (ASCs). IC immunized mice had significantly higher PRV-specific serum Abs and neutralizing Abs titers than SC immunized mice. Spleen and cervical lymph nodes (CLNs) of IC immunized mice produced significantly more PRV-specific Abs than that of SC immunized mice. ASCs, immunoglobulin and mRNAs of IgG, CXCL9, 10, 13 and BAFF were predominantly detected in the brain of IC immunized mice, but not in SC immunized mice. IC immunized mice (86%) survived more than subcutaneously (SC) immunized mice (33%) by suppression of virus propagation, when PRV was inoculated directly into the brain. In conclusion, IC immunization induced more effective immune responses to protect the CNS from PRV infection by attracting ASCs into the CNS and inducing much more PRV-specific serum neutralizing Abs. This approach may have important implications as a novel treatment procedure for neurotropic virus infections in both humans and animals.
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PMID:Experimental intracerebral vaccination protects mouse from a neurotropic virus by attracting antibody secreting cells to the CNS. 2164 47

Previous studies have reported activation of the B cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system in T independent immunity against malaria infection. Plasmodium falciparum (P. falciparum) infected animal model is not feasible. Therefore, little is known about the occurrence of BAFF/APRIL system and changes in falciparum lymphoid tissues. This study aimed to investigate the expression of BAFF/APRIL system components in lymphoid tissues from P. falciparum infected patients. Spleen and lymph node samples from 14 patients were collected at autopsy. Normal spleens and bacterially infected tonsils served as controls. The protein and/or mRNA expression of BAFF/APRIL and their cognate receptors, BAFF-R, TACI and BCMA, were determined by immunohistochemistry and RT-qPCR, respectively. The spleens of the patients exhibited significantly higher BAFF-R protein expression than normal spleens. Although without appropriate control, BCMA protein was markedly observed only in the lymph nodes. BAFF and BCMA mRNA levels were also significantly elevated in the spleen tissues of the patients compared with normal spleens. The overall BAFF-R protein levels in the lymphoid tissues of the patients correlated positively with parasitaemia. These findings are the first to confirm that BAFF/APRIL system activation in lymphoid tissues and is positively correlated with the parasitaemia levels in falciparum malaria.
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PMID:The activation of BAFF/APRIL system in spleen and lymph nodes of Plasmodium falciparum infected patients. 3212 65