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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin-infiltrating T lymphocytes are thought to play a major role in the pathogenesis of cutaneous lupus erythematosus (CLE). In this study, we investigated the role of the chemokine receptor 4 (CCR4) and its ligand thymus- and activation-regulated chemokine (TARC/CCL17) for the recruitment of T cells in inflamed skin of patients with CLE. We found significant numbers of CCR4+ T lymphocytes in the skin of all patients with CLE. Interestingly, a subset of patients with disseminated scarring skin involvement were characterized by both lesional and circulating CD8+ T cells expressing CCR4. Destruction of epidermal and adnexal structures was histomorphologically associated with CCR4+ cytotoxic T cells invading basal layers of the epidermis where keratinocytes showed apoptotic death. The CCR4 ligand TARC/CCL17 was strongly expressed in skin lesions and elevated in the serum of CLE patients. The functional relevance of lymphocytic CCR4 expression could be confirmed by TARC/CCL17-specific in vitro migration assays. Our investigations suggest that CCR4 and TARC/CCL17 play a role in the pathophysiology of CLE. In particular, cytotoxic CD8+ T cells expressing CCR4 appear to be involved in scarring subtypes of CLE.
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PMID:Role of the chemokine receptor CCR4 and its ligand thymus- and activation-regulated chemokine/CCL17 for lymphocyte recruitment in cutaneous lupus erythematosus. 1595

Following tetanus vaccination, a wave of antibody-secreting cells appear in the peripheral blood composed of vaccine-specific, migratory plasmablasts and plasma cells secreting antibodies specific for other antigens. The latter probably were tissue resident plasma cells formed in earlier immune responses that are mobilized due to competition with the newly formed tetanus-specific plasmablasts. Newly formed plasma cells secreting antibodies specific for a particular antigen/vaccine are accommodated in the bone marrow likely at the global expense of the pre-existing long-lived plasma cell population providing humoral memory for other antigens. Plasmablasts but not mature plasma cells are attracted by the ligands for the chemokine receptors CXCR4 and CXCR3. While CXCR4 and its cognate ligand is important for plasma cell homing to the bone marrow, CXCR3 and its ligand IP10 are likely to be involved in attracting them to inflamed tissue. In NZB/W mice, a model for systemic lupus, long-lived autoreactive plasma cells are present not only in bone marrow, but also in inflamed tissues and spleen. Autoreactive plasma cells in the spleen are present long before the onset of the disease, suggesting that these cells contribute to induction of immunopathology.
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PMID:Long-lived plasma cells in immunity and immunopathology. 1628 Jan 69

Although multiple studies suggest a potential role for angiotensin II in inflammation, most were performed either in vitro or in animals with non-immune-complex-mediated diseases. Extrapolation of these findings to humans, particularly patients with lupus, which involves multiple immunoregulatory pathways, is unclear. In autoimmune-prone MRL/lpr mice, angiotensin-converting-enzyme (ACE) inhibition improved survival although to a lesser degree than cyclophosphamide and diminished the glomerular histopathologic damage, proteinuria, lymphoid hyperplasia, dermatitis, and hypergammaglobulinemia, with a reduction in TGF-beta1 and beta 2 expression in the kidneys and renal chemokine mRNA expression. Spleen levels of IL-4 and IL-10 were also reduced. Uncontrolled studies in patients with treatment-refractory lupus nephritis showed a significant reduction in proteinuria with ACE-inhibitors and Angiotensin receptor blockers treatment. The 'masking' effect of ACE-inhibitors should be taken into consideration, as an exacerbation of lupus nephritis may be missed when estimated by the magnitude of proteinuria, which is decreased by these treatments. No single ACE genotype was consistently associated with subsets of SLE patients. In retrospective analyses, ACE-inhibitor use predicted a favourable outcome in 94 cases of pauci-immune vasculitis. The attenuating effect of angiotensin II inhibitors on the progression of chronic renal disease is well recognized. The data on the role of this intervention in lupus is limited.
Lupus 2006
PMID:The renin-angiotensin system in lupus: physiology, genes and practice, in animals and humans. 1683 Aug 77

Systemic lupus erythematosus (SLE) is a serious systemic autoimmune disease of unknown etiology. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is operative in innate and adaptive immunity and important in immune-mediated diseases such as rheumatoid arthritis and atherosclerosis. The functional relevance of MIF in systemic autoimmune diseases such as SLE is unknown. Using the lupus-prone MRL/lpr mice, we aim to examine the expression and function of MIF in this murine model of systemic autoimmune disease. These experiments revealed that renal MIF expression was significantly higher in MRL/lpr mice compared with nondiseased control mice (MRL/MpJ), and MIF was also markedly up-regulated in skin lesions of MRL/lpr mice. To examine the effect of MIF on development of systemic autoimmune disease, we generated MRL/lpr mice with a targeted disruption of the MIF gene (MIF(-/-)MRL/lpr), and compared their disease manifestations to MIF(+/+)MRL/lpr littermates. MIF(-/-)MRL/lpr mice exhibited significantly prolonged survival, and reduced renal and skin manifestations of SLE. These effects occurred in the absence of major changes in T and B cell markers or alterations in autoantibody production. In contrast, renal macrophage recruitment and glomerular injury were significantly reduced in MIF(-/-)MRL/lpr mice, and this was associated with reduction in the monocyte chemokine MCP-1. Taken together, these data suggest MIF as a critical effector of organ injury in SLE.
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PMID:Macrophage migration inhibitory factor deficiency attenuates macrophage recruitment, glomerulonephritis, and lethality in MRL/lpr mice. 1701 58

Pro-inflammatory chemokines are important mediators of inflammation and autoimmune injury. The spatial and temporal expression of chemokines and chemokine receptors in the nephritic kidney suggests that targeting the chemokine system may represent a valuable approach for anti-inflammatory therapy of lupus nephritis. In this review we summarize the available data on the pathogenic role of chemokines and chemokine receptors in lupus nephritis and particularly focus on epidemiological data in lupus patients and interventional studies with chemokine or chemokine receptor antagonists in experimental lupus.
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PMID:Blockade of chemokine-mediated tissue injury in lupus nephritis. 1721 77

The clinical and histological presentation of inflammatory disease in the skin is exceedingly heterogeneous. Nonetheless, most inflammatory dermatoses can be classified according to five stereotypical tissue-reaction patterns: the spongiotic, the lichenoid, the psoriasiform, the vesiculo-bullous and the vasculopathic. By means of potent antigen-presenting cells, cytokine and chemokine cascades and a skin-specific cutaneous lymphocyte antigen (CLA)-positive lymphocyte population, the skin is able to respond very efficiently to pathogens that threaten the individual. Inflammatory skin diseases follow the rules and routes of the physiological reaction to inflammation but however for various reasons the immune response may be inadequate, enhanced or chronic. In allergic contact dermatitis, which is a prototype of the spongiotic reaction pattern, the inflammation is directed against an otherwise harmless antigen, for which the body is sensibilized. Lichenoid dermatitis (like erythema multiforme, graft versus host disease or lupus erythematodes) is based on a primary cytotoxic reaction against the basal epithelial cell, due to alterations in its antigenic make-up or due to an altered immune response. In psoriasis, an example of psoriasiform dermatitis, the interaction between inflammatory cells, antigen presenting cells and epithelial cells is disturbed.
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PMID:[The immune system of the skin and stereotyped reaction patterns in inflammatory skin diseases]. 1722 34

Glomerulonephritis is an important cause of end-stage renal failure, yet the pathogenetic mechanisms of most forms of glomerulonephritis are not clear. Renal fibrosis is the final common pathway for many kidney lesions that lead to chronic progressive organ failure. Recent study suggests that chemokines and chemokine receptors are involved in the resolution or progression of renal diseases. In view of the above we detected using immunohistochemistry the expression of RANTES, CCR5+ cells,TGF-beta1, alpha-SMA in renal biopsy specimens in 17 patients with IVG A/C class of lupus nephritis and in 10 normal kidneys. The correlative study was undertaken to evaluate the possible relationships between the immunoexpression of RANTES, the number of CCR5+ cells, the immunoexpression of TGF-beta1, alpha-SMA, the value of interstitial cortical volume and the serum creatinine level in patients with lupus nephropathy. Statistical analysis revealed significant increase in tubulointerstitial RANTES immunoexpression in lupus nephritis as compared to normal controls. In our study CCR5+ cells were detected in the interstitium in tissue samples in patient with lupus nephritis, meanwhile no CCR5+ cells were documented in normal controls. We found a strong positive correlation between tubulointerstitial immunoexpression of RANTES and the number of interstitial CCR5+ cells as well as between immunoexpression of RANTES and the immunoexpression of TGF-beta1, alpha-SMA, renal cortical volume and serum creatinine in patients with lupus nephritis. Moreover, the number of interstitial CCR5+ cells was positively correlated with tubulointerstitial alpha-SMA immunoexpression and renal cortical volume. In summary, the results suggest that in lupus nephritis RANTES may participate in interstitial lesions via CCR5+ cells.
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PMID:The significant role of RANTES and CCR5 in progressive tubulointerstitial lesions in lupus nephropathy. 1758 40

Over the past decade, accumulating evidence has indicated a crucial role for chemokines and chemokine receptors in the pathogenesis of autoimmune diseases in both human and mouse models. Locally secreted chemokines and their receptors are important mediators of leukocyte recruitment to the tissues, and contribute to the initiation and progression of autoimmune diseases. Thus, blockade of chemokine and chemokine receptor interactions has emerged as a novel therapeutic strategy. MRL/MpJ-lpr/lpr (MRL/lpr) and (NZB X NZW) F1 mice, the two strains of mice that develop spontaneous autoimmune disease closely resembling human systemic lupus erythematosus (SLE), are considered to be excellent models for investigating the pathogenesis of the human disease. In addition, similar expression patterns of chemokines and chemokine receptors in inflamed organs are shown in humans and lupus model mice, especially MRL/lpr mice. Therefore, findings obtained from experiments with lupus model mice may be applicable to the treatment of these autoimmune diseases in humans. In this article, we review the role of chemokines and chemokine receptors involved in the pathogenesis of autoimmune diseases and the therapeutic approach of chemokine blockade in lupus model mice.
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PMID:Chemokine blockade for lupus model mice. 1798 62

Recent studies have revealed new populations of T/B cells, including central/effector memory, follicular T cells and CXCR3+ or CXCR4+ B cells. In the present study, changes in these populations of CD4+ T cells were examined on the basis of the expression of CD62L, CCR7 and CXCR5 in patients with systemic lupus erythematosus (SLE) in relation to CCL21 and CXCL10. Changes in CXCR3+, CXCR4+ and CXCR5+ B cells were also examined. CD62L and various chemokine receptors were examined by flow cytometry analysis using monoclonal antibodies, and CCL21 and CXCL10 were examined by sandwich enzyme-linked immunosorbent assay. In patients with SLE, a decrease of naive T cells and an increase in the ratio of activated effector memory T cells were associated with an increase of CCL21 and CXCL10 in serum, although the correlation was not significant. An increase in the ratio of CXCR3+ B cells was also recognized. These results suggest that naive T cells are transferred to lymphoid tissue by CCL21, and that effector memory T cells are activated by CXCL10. It is also suggested that B cells responsive to follicular helper T cells tend to migrate to inflammatory tissue.
Lupus 2008 Jan
PMID:Striking alteration of some populations of T/B cells in systemic lupus erythematosus: relationship to expression of CD62L or some chemokine receptors. 1808 80

To elucidate the molecular mechanism of glomerular events in lupus nephritis, we performed genome-wide mRNA expression analysis of glomeruli microdissected from lupus mice. MRL/lpr mice (12-week-old) were orally given vehicle or prednisolone (10 mg/kg per day) for 4 weeks. Renal histology of MRL/lpr mice revealed mesangial proliferative glomerulonephritis with cellular infiltration of macrophages, T cells, and neutrophils. We identified 567 up-regulated genes in MRL/lpr glomeruli compared to control congenic mice. Those included complement components, adhesion molecules, chemokines and their receptors, and molecules related to antigen presentation. Over 130 genes were considered preferentially or exclusively expressed in hematopoietic cell lineages possibly reflecting leukocytes accumulation. Of note is the finding that chemokines and chemokine receptors (CCL3, CCL4, CCL5, CXCL9, CXCL10, CXCL11, CXCL16, CCR5, CXCR3, and CXCR6) that are related to T helper 1 (Th1) cells accumulation were up-regulated concomitantly with increased expression of Ebi3, a subunit of IL-27 that plays a role in Th1 predominance. These changes were accompanied by increased mRNA expression of many genes that were inducible by Th1 cytokine interferon-gamma. Prednisolone markedly attenuated glomerular lesion and leukocyte influx parallel with the reduction of enhanced gene expression. The present study shows additional evidence supporting glomerular Th1 cells accumulation and their role. Our data also provide an important resource in seeking new therapeutic targets to lupus nephritis. Supplemental table: available only at http://dx.doi.org/10.1254/jphs.FP0071337.
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PMID:Microarray analysis of glomerular gene expression in murine lupus nephritis. 1818 31


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