BCA-1/CXCL13 expression is associated with CXCR5-positive B-cell cluster formation in acute renal transplant rejection

Steinmetz, Oliver M.; Panzer, Ulf; Kneissler, U.; Harendza, Sigrid; Lipp, Martin; Helmchen, Udo; Stahl, Rolf A.K.

doi:10.1111/j.1523-1755.2005.00244.x

Cited by 71 publications

(84 citation statements)

References 20 publications

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“…In various disease models, ectopic expression of CXCL13 has been reported in vascular endothelium of the CNS (51, 52) as well as in germinal centers of ectopic lymphoid follicles within the synovium of chronic arthritis patients (53-57). Furthermore, it has been observed recently that CXCL13 expression can be colocalized to B cell cluster formations in rejecting human renal grafts (58). In general, these studies suggest that CXCL13 expression may be associated with development of diseases.…”

Section: Discussionmentioning

confidence: 68%

CXCR5/CXCL13 Interaction Is Important for Double-Negative Regulatory T Cell Homing to Cardiac Allografts

Lee

Chen

Shi

et al. 2006

The Journal of Immunology

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Accumulating evidence indicates that regulatory T (Treg) cells control development of various diseases both systemically and locally. However, molecular mechanisms involved in Treg cell homing remain elusive. We have shown previously that αβTCR+CD3+CD4−CD8− double-negative (DN) Treg cells selectively accumulate in tolerant allografts to maintain localized immune regulation. However, the molecular mechanism leading to the accumulation of DN Treg cells in tolerant grafts was not known. Our cDNA microarray analysis revealed significant up-regulation of chemokine receptor CXCR5 mRNA in DN Treg clones compared with nonregulatory clones. In this study, we examined the importance of CXCR5 in mediating DN Treg migration. Compared with CD4 and CD8 T cells, both primary DN Treg cells and clones constitutively express high levels of CXCR5 protein, enabling them to migrate toward increasing CXCL13 gradients in vitro. After infusion into recipient mice, CXCR5+ DN Treg clones, but not their CXCR5− mutants, preferentially accumulated in cardiac allografts and could prevent graft rejection. Furthermore, we found that allogeneic cardiac allografts express high levels of CXCL13 mRNA compared with either recipient native hearts or nontransplanted donor hearts. Ab neutralization of CXCL13 abrogated DN Treg cell migration in vitro and prevented in vivo homing of DN Treg clones into allografts. These data demonstrate that DN Treg cells preferentially express CXCR5, and interaction of this chemokine receptor with its ligand CXCL13 plays an important role in DN Treg cell migration both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 68%

CXCR5/CXCL13 Interaction Is Important for Double-Negative Regulatory T Cell Homing to Cardiac Allografts

Lee

Chen

Shi

et al. 2006

The Journal of Immunology

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“…Breast cancer cells might interact through CXCR5/CXCL13 interactions to organise cellular cluster formation and compartmentalisation as has been shown for B cells in renal allografts (Steinmetz et al, 2005) and in salivary glands of patients with Sjogren's syndrome (Barone et al, 2005). This way, CXCL13 and its ligand might contribute significantly to tumour formation, and therapeutic interventions aiming at interrupting CXCL13/ CXCR5 interactions might be of benefit for the clinical course of patients with breast cancer.…”

Section: Discussionmentioning

confidence: 93%

Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients

et al. 2008

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The abilities of chemokines in orchestrating cellular migration are utilised by different (patho-)biological networks including malignancies. However, except for CXCR4/CXCL12, little is known about the relation between tumour-related chemokine expression and the development and progression of solid tumours like breast cancer. In this study, microarray analyses revealed the overexpression of chemokine CXCL13 in breast cancer specimens. This finding was confirmed by real-time polymerase chain reaction in a larger set of samples (n ¼ 34) and cell lines, and was validated on the protein level performing Western blot, ELISA, and immunohistochemistry. Levels of CXCR5, the receptor for CXCL13, were low in malignant and healthy breast tissues, and surface expression was not detected in vitro. However, we observed a strong (P ¼ 0.0004) correlation between the expressions of CXCL13 and CXCR5 in breast cancer tissues, indicating a biologically relevant role of CXCR5 in vivo. Finally, we detected significantly elevated serum concentrations of CXCL13 in patients with metastatic disease (n ¼ 54) as compared with controls (n ¼ 44) and disease-free patients (n ¼ 48). In conclusion, CXCL13 is overexpressed within breast cancer tissues, and increased serum levels of this cytokine can be found in breast cancer patients with metastatic disease pointing to a role of CXCL13 in the progression of breast cancer, suggesting that CXCL13 might serve as a useful therapeutic target and/or diagnostic marker in this malignancy.

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“…CXCL13 is found in ectopic lymphoid tissues in other inflammatory diseases and has been associated with focal B cell infiltrates in some diseases (15,16) and with accumulation of CD4-positive T cells in others (17). The CXCL13 receptor CXCR5 was expressed predominantly by B cells in the NZB/W kidney.…”

Section: Discussionmentioning

confidence: 99%

Activated Renal Macrophages Are Markers of Disease Onset and Disease Remission in Lupus Nephritis

Schiffer¹,

Bethunaickan

Ramanujam

et al. 2008

The Journal of Immunology

207

174

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Costimulatory blockade with CTLA4Ig and anti-CD40L along with a single dose of cyclophosphamide induces remission of systemic lupus erythematosus nephritis in NZB/W F1 mice. To understand the mechanisms for remission and for impending relapse, we examined the expression profiles of 61 inflammatory molecules in the perfused kidneys of treated mice and untreated mice at different stages of disease. Further studies using flow cytometry and immunohistochemistry allowed us to determine the cellular origins of several key markers. We show that only a limited set of inflammatory mediators is expressed in the kidney following glomerular immune complex deposition but before the onset of proteinuria. Formation of a lymphoid aggregate in the renal pelvis precedes the invasion of the kidney by inflammatory cells. Regulatory molecules are expressed early in the disease process and during remission but do not prevent the inevitable progression of active inflammation. Onset of proliferative glomerulonephritis and proteinuria is associated with activation of the renal endothelium, expression of chemokines that mediate glomerular cell infiltration, and infiltration by activated dendritic cells and macrophages that migrate to different topographical areas of the kidney but express a similar profile of inflammatory cytokines. Increasing interstitial infiltration by macrophages and progressive tubular damage, manifested by production of lipocalin-2, occur later in the disease process. Studies of treated mice identify a type II (M2b)-activated macrophage as a marker of remission induction and impending relapse and suggest that therapy for systemic lupus erythematosus nephritis should include strategies that prevent both activation of monocytes and their migration to the kidney.

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BCA-1/CXCL13 expression is associated with CXCR5-positive B-cell cluster formation in acute renal transplant rejection

Cited by 71 publications

References 20 publications

CXCR5/CXCL13 Interaction Is Important for Double-Negative Regulatory T Cell Homing to Cardiac Allografts

CXCR5/CXCL13 Interaction Is Important for Double-Negative Regulatory T Cell Homing to Cardiac Allografts

Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients

Activated Renal Macrophages Are Markers of Disease Onset and Disease Remission in Lupus Nephritis

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