Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TALL-1 is a member of the tumor necrosis factor family that binds to BCMA, TACI, and BAFF-R, three receptors mostly expressed by mature B lymphocytes. Previous studies have shown that the TALL-1 signaling is critically involved in B cell proliferation, maturation, and progression of lupus-like, autoimmune diseases. In this report, we performed cDNA subtractive hybridization experiments to identify downstream genes up-regulated by TALL-1. These experiments indicated that 10 genes, including interleukin (IL)-10, lymphocyte activation gene-1 (LAG-1), GCP-2, PBEF, ferritin, PIM-2, TFG, CD27 ligand, DUSP5, and archain, were up-regulated at the mRNA level by TALL-1 stimulation in B lymphoma RPMI-8226 cells and/or primary B lymphocytes. We also demonstrated that TALL-1 activated transcription of IL-10 and LAG-1 in a nuclear factor-kappaB-dependent manner in reporter gene assays. Moreover, our findings indicated BAFF-R, but not TACI, could dramatically up-regulate IL-10 secretion by RPMI-8226 cells. The identification of TALL-1-up-regulated genes will help explain the mechanisms of TALL-1-triggered biological and pathological effects and to identify molecular targets for intervention of lupus-like autoimmune diseases.
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PMID:Identification of downstream genes up-regulated by the tumor necrosis factor family member TALL-1. 1214 33

Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance. A hallmark of SLE is the presence of autoantibodies resulting from B cell hyperactivity. Previous studies have shown that the presence of abnormal B cell subsets in the periphery, such as CD27highCD20- B cells, correlate with disease activity. We examined the relationship between the expression of CD70, the ligand for CD27 expressed by activated T cells, and indicators of disease activity. A significant increase in median CD70+CD4+ T cell frequencies and memory CD45RA-CD4+ T cell frequencies was observed in SLE samples as compared to healthy controls. The frequencies of CD70+CD4+ T cells correlated with disease duration but not age, treatment, or disease activity. Although a majority of CD70+CD4+ T cells appeared to be effector memory cells, mitogen-stimulated CD70+CD4+ T cells were capable of secreting a full repertoire of effector cytokines. Despite the presence of activated CD4+ T cells, no increase in immunosenescent CD4+ T cells, as defined by the loss of CD28 and/or the acquisition of CD57 was observed in samples from SLE patients. These studies indicate that increased CD70 expression might serve as a useful marker of abnormal T cell activity in SLE.
Lupus 2005
PMID:Increased prevalence of activated CD70+CD4+ T cells in the periphery of patients with systemic lupus erythematosus. 1617 31