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)

The expression of muH chain is an important checkpoint in B cell development. In mice deficient for IgM transmembrane tail exons (muMT mice) B cell development is blocked at the pro-B stage. However, we showed that Fas-deficient muMT mice (muMT/lpr) develop a very small population of isotype-switched B cells and produce high titers of self-reactive serum antibodies. In addition, muMT/lpr mice develop severe lymphoproliferation and both pathologic processes occur at young ages. This may suggest that lack of Fas-Fas ligand signaling exacerbates murine lupus in B cell lymphopenic mice. To test this we analyzed antibody and plasma cell formation, and accumulation of abnormal T cells in muMT/lpr mice. Our results show that the muMT/lpr mouse is particularly permissive for the development and accumulation of antibody-producing cells, thereby explaining the high titers of serum antibodies in these mice. In addition, we found that accumulating cells in spleen and lymph nodes of muMT/lpr mice are alphabeta T cells expressing the abnormal B220+/CD3+ surface markers, a phenotype also described for other Fas-deficient mouse models. Strikingly, we found that accumulating cells in muMT/lpr mice express the membrane proteoglycan syndecan-1, a known plasma cell marker. Development of these cells is blocked in mice deficient for TCRbeta and TCRdelta. We also found that both antibody production and lymphoproliferation in muMT/lpr mice are Th1 regulated. Our results, therefore, suggest that in the muMT/lpr mouse model a small population of isotype-switched B cells is sufficient for the initiation and propagation of Th1-regulated murine lupus.
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PMID:Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Igmu-deficient/lpr mice. 1291 56

The unfolded protein response (UPR) is a stress response pathway that is driven by the increased load of unfolded proteins in the endoplasmic reticulum of highly secretory cells such as plasma cells (PCs). X box binding protein 1 (XBP1) is a transcription factor that mediates one branch of the UPR and is crucial for the development of antibody-secreting PCs. PCs represent only one class of terminally differentiated B cells, however, and little is known about the role for XBP1 in the other class: memory B cells. We have developed an XBP1(fl/fl) CD19(+/cre) conditional knockout (XBP1(CD19)) mouse to build upon our current understanding of the function of XBP1 in PC differentiation as well as to explore the role of XBP1 in memory cell development. Using this model, we show that XBP1(CD19) mice are protected from disease in an autoantibody-mediated mouse lupus model. We also identify a novel developmental stage at which B cells express the traditional PC marker CD138 (syndecan-1) but have yet to undergo XBP1-dependent functional and morphological differentiation into antibody-secreting cells. Finally, we show that memory B cells develop normally in XBP1(CD19) mice, demonstrating that XBP1-mediated functions occur independently of any memory cell lineage commitment.
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PMID:XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development. 1975 83

The aim of the study was to assess the serum levels of Syndecan-1 in a group of Egyptian juvenile systemic lupus erythematosus (JSLE) patients and to study any possible associations with disease activity, renal activity and organ damage. Serum level of Syndecan-1 was assessed in 60 Egyptian JSLE patients and 30 apparently healthy age and gender matched children using ELISA. SLE Disease Activity Index-2000 (SLEDAI-2K), renal SLEDAI-2K, renal activity score and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index were assessed for all patients. Serum SDC-1 levels were higher in patients with JSLE than in healthy controls (p<0.001) and were positively correlated with SLEDAI-2K (p<0.001), with renal SLEDAI score (p=0.008) and renal activity score (p=0.04). So, Syndecan-1 might be used as a marker for disease activity and renal activity in JSLE patients.
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PMID:Study of serum syndecan-1 levels in a group of Egyptian juvenile systemic lupus erythematosus patients. 2783 71

Expansion of autoreactive follicular helper T (Tfh) cells is tightly restricted to prevent induction of autoantibody-dependent immunological diseases, such as systemic lupus erythematosus (SLE). Here we show expression of an orphan immune regulator, death receptor 6 (DR6/TNFRSF21), on a population of Tfh cells that are highly expanded in lupus-like disease progression in mice. Genome-wide screening reveals an interaction between syndecan-1 and DR6 resulting in immunosuppressive functions. Importantly, syndecan-1 is expressed specifically on autoreactive germinal centre (GC) B cells that are critical for maintenance of Tfh cells. Syndecan-1 expression level on GC B cells is associated with Tfh cell expansion and disease progression in lupus-prone mouse strains. In addition, Tfh cell suppression by DR6-specific monoclonal antibody delays disease progression in lupus-prone mice. These findings suggest that the DR6/syndecan-1 axis regulates aberrant GC reactions and could be a therapeutic target for autoimmune diseases such as SLE.
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PMID:Death receptor 6 contributes to autoimmunity in lupus-prone mice. 2810 Sep 25