GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 8 ( 2015-04-15), p. 3646-3655
    Abstract: Mouse experimental autoimmune glomerulonephritis, a model of human antiglomerular basement membrane disease, depends on both Ab and T cell responses to the Goodpasture Ag noncollagenous domain 1 of the α3-chain of type IV collagen (α3IV-NC1). The aim of our study was to further characterize the T cell–mediated immune response. Repeated immunization with mouse α3IV-NC1 caused fatal glomerulonephritis in DBA/1 mice. Although two immunizations were sufficient to generate high α3IV-NC1–specific IgG titers, Ab and complement deposition along the glomerular basement membranes, and a nephrotic syndrome, two additional immunizations were needed to induce a necrotizing/crescentic glomerulonephritis. Ten days after the first immunization, α3IV-NC1–specific CD4+ cells producing TNF-α, IFN-γ, or IL-17A were detected in the spleen. With the emergence of necrotizing/crescentic glomerulonephritis, ∼0.15% of renal CD4+ cells were specific for α3IV-NC1. Using peptides spanning the whole α3IV-NC1 domain, three immunodominant T cell epitopes were identified. Immunization with these peptides did not lead to clinical signs of experimental autoimmune glomerulonephritis or necrotizing/crescentic glomerulonephritis. However, mice immunized with one of the peptides (STVKAGDLEKIISRC) developed circulating Abs against mouse α3IV-NC1 first detected at 8 wk, and 50% of the mice showed mild proteinuria at 18–24 wk due to membranous glomerulopathy. Taken together, our results suggest that autoreactive T cells are able to induce the formation of pathologic autoantibodies. The quality and quantity of α3IV-NC1–specific Ab and T cell responses are critical for the phenotype of the glomerulonephritis.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2015
    detail.hit.zdb_id: 1475085-5
    detail.hit.zdb_id: 3056-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 181, No. 9 ( 2008-11-01), p. 6546-6556
    Abstract: The chemokine receptor CCR5 is predominantly expressed on monocytes and Th1-polarized T cells, and plays an important role in T cell and monocyte recruitment in inflammatory diseases. To investigate the functional role of CCR5 in renal inflammation, we induced a T cell-dependent model of glomerulonephritis (nephrotoxic serum nephritis) in CCR5−/− mice. Induction of nephritis in wild-type mice resulted in up-regulation of renal mRNA expression of the three CCR5 chemokine ligands, CCL5 (15-fold), CCL3 (4.9-fold), and CCL4 (3.4-fold), in the autologous phase of the disease at day 10. The up-regulated chemokine expression was paralleled by infiltration of monocytes and T cells, followed by renal tissue injury, albuminuria, and loss of renal function. Nephritic CCR5−/− mice showed a 3- to 4-fold increased renal expression of CCL5 (61.6-fold vs controls) and CCL3 (14.1-fold vs controls), but not of CCL4, in comparison with nephritic wild-type mice, which was accompanied by augmented renal T cell and monocyte recruitment and increased lethality due to uremia. Furthermore, CCR5−/− mice showed an increased renal Th1 response, whereas their systemic humoral and cellular immune responses were unaltered. Because the CCR5 ligands CCL5 and CCL3 also act via CCR1, we investigated the effects of the pharmacological CCR1 antagonist BX471. CCR1 blockade in CCR5−/− mice significantly reduced renal chemokine expression, T cell infiltration, and glomerular crescent formation, indicating that increased renal leukocyte recruitment and consecutive tissue damage in nephritic CCR5−/− mice depended on functional CCR1. In conclusion, this study shows that CCR5 deficiency aggravates glomerulonephritis via enhanced CCL3/CCL5-CCR1-driven renal T cell recruitment.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2008
    detail.hit.zdb_id: 1475085-5
    detail.hit.zdb_id: 3056-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 183, No. 7 ( 2009-10-01), p. 4693-4704
    Abstract: Infiltration of T cells into the kidney is a typical feature of human and experimental lupus nephritis that contributes to renal tissue injury. The chemokine receptor CXCR3 is highly expressed on Th1 cells and is supposed to be crucial for their trafficking into inflamed tissues. In this study, we explored the functional role of CXCR3 using the MRL/MpJ-Faslpr (MRL/lpr) mouse model of systemic lupus erythematosus that closely resembles the human disease. CXCR3−/− mice were generated and backcrossed into the MRL/lpr background. Analysis of 20-wk-old CXCR3−/− MRL/lpr mice showed amelioration of nephritis with reduced glomerular tissue damage and decreased albuminuria and T cell recruitment. Most importantly, not only the numbers of renal IFN-γ-producing Th1 cells, but also of IL-17-producing Th17 cells were significantly reduced. Unlike in inflamed kidneys, there was no reduction in the numbers of IFN-γ- or IL-17-producing T cells in spleens, lymph nodes, or the small intestine of MRL/lpr CXCR3−/− mice. This observation suggests impaired trafficking of effector T cells to injured target organs, rather than the inability of CXCR3−/− mice to mount efficient Th1 and Th17 immune responses. These findings show a crucial role for CXCR3 in the development of experimental lupus nephritis by directing pathogenic effector T cells into the kidney. For the first time, we demonstrate a beneficial effect of CXCR3 deficiency through attenuation of both the Th1 and the newly defined Th17 immune response. Our data therefore identify the chemokine receptor CXCR3 as a promising therapeutic target in lupus nephritis.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2009
    detail.hit.zdb_id: 1475085-5
    detail.hit.zdb_id: 3056-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Arthritis & Rheumatology, Wiley, Vol. 67, No. 2 ( 2015-02), p. 475-487
    Abstract: The CD4+ T cell immune response plays a pivotal role in the immunopathogenesis of human and experimental lupus nephritis, but the contribution of the Th17/interleukin‐17 (IL‐17) immune pathway to renal tissue injury in systemic lupus erythematosus (SLE) remains to be elucidated. The aim of this study was to characterize the function of the Th17/IL‐17A immune response in 2 murine models of lupus nephritis. Methods IL‐17A–deficient MRL/MPJ‐Fas lpr /2J (MRL/ lpr ) mice were generated, and the clinical course of nephritis was monitored by assessing the levels of albuminuria, extent of renal tissue injury, and functional parameters. In addition, lupus‐prone (NZB × NZW)F1 (NZB/NZW) mice were treated with anti–IL‐17A and anti–interferon‐γ (anti‐IFNγ) antibodies, and their effects on the clinical course of lupus nephritis were assessed. Results Characterization of renal IL‐17A–producing and IFNγ‐producing T cells in MRL/ lpr and NZB/NZW mice revealed low numbers of infiltrating CD3+IL‐17A+ cells. Renal IL‐17A was mainly produced by CD4/CD8 double‐negative CD3+ T cells and CD4+ Th17 cells. In contrast, the number of renal CD3+IFNγ+ cells continuously increased over time and largely consisted of typical CD4+ Th1 cells. IL‐17A deficiency did not affect the morphologic or functional parameters in MRL/ lpr mice with lupus nephritis, nor did IL‐17A neutralization affect the clinical course of nephritis in NZB/NZW mice, but anti‐IFNγ treatment attenuated the severity of the disease. Conclusion The Th17/IL‐17A immune response plays no major role in the immunopathogenesis of lupus nephritis in MRL/ lpr and NZB/NZW mice. Thus, the results of this study do not support the hypothesis that IL‐17A targeting could be an intriguing new therapeutic approach for the management of proliferative lupus nephritis in SLE patients.
    Type of Medium: Online Resource
    ISSN: 2326-5191 , 2326-5205
    URL: Issue
    RVK:
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 127294-9
    detail.hit.zdb_id: 2754614-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...