Immunohistochemical characterization of synovial cells in arthritic mrl‐lpr/lpr mice

Tarkowski, Andrej; Jönsson, Roland; Holmdahl, Rikard; Klareskog, Lars

doi:10.1002/art.1780300110

Cited by 38 publications

(13 citation statements)

References 37 publications

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“…In approximately 20% female MRL/ lpr mice at 12 weeks of age, any slight findings such as hyperplasia of synovial cells and mononuclear cell infiltration were observed. These findings of arthritis lesions in MRL/ lpr mice are consistent with those in previously demonstrated reports [50]–[53].…”

Section: Methodssupporting

confidence: 93%

Fas-Independent T-Cell Apoptosis by Dendritic Cells Controls Autoimmune Arthritis in MRL/lpr Mice

et al. 2012

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BackgroundAlthough autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated dendritic cells (DCs) play a key role in the pathogenesis of rheumatoid arthritis (RA) in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity.Methods and FindingCellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4+ T, B, and CD4−CD8− double negative (DN) T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice.ConclusionThese results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice.

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Section: Methodssupporting

confidence: 93%

Fas-Independent T-Cell Apoptosis by Dendritic Cells Controls Autoimmune Arthritis in MRL/lpr Mice

et al. 2012

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“…Thus, in the MRL lpr/lpr mice the proliferating and infiltrating synovial cells to a large extent carried macrophage markers. However, most of these cells were negative for MHC class II expression and virtually no T cells could be detected close to the synovial lining or in the pannus either by conventional histology [71] or after immunohistochemical stainirlgs with the Lyt-1, anti-CD4 or anti-CD8 antibodies [83]; in parallel studies it was demonstrated that the applied methods were indeed sensitive enough to detect those T cells of these mice that display a low staining for these markers (the ,,dull" cells) [83]. It was concluded from these studies that the local pathogenetic process of MRL lpr/lpr mice differ from that of RA concerning the working hypothesis of a local and class II MHC-driven T cell activation and over-expression of MHC class II.…”

Section: Arthritis In Mrl Lpr/lpr Micementioning

confidence: 98%

What can we learn about rheumatoid arthritis from animal models?

Klareskog

1989

Springer Semin Immunopathol

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“…The synovium is infiltrated by large numbers of transformed-appearing mesenchymal cells at the cartilage-pannus junction which express the macrophage marker Mac-1. Interestingly, class II expression by these cells is scarce and lymphocytes are completely absent or at a site distant from the foci of bone and cartilage erosion [72].…”

Section: Animal Modelsmentioning

confidence: 98%

Potential mechanisms for coordinate gene activation in the rheumatoid synoviocyte: Implications and hypotheses

Ritchlin

Winchester

1989

Springer Semin Immunopathol

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Evidence is reviewed to support the concept that synovial cells in rheumatoid arthritis have undergone distinctive alterations at the cellular and subcellular level that result in their taking on some of the characteristics that are also manifest by transformed cells. These phenotypic modulations could be indirectly driven by cytokines in a paracrine or autocrine fashion. Specific regional patterns of cell phenotype modulation were used to argue against a simple widely diffusing direct inductive effect to cytokines and in favor of microenvironmental determinants. It is hypothesized that these extracellular factors induce novel activation in a coordinate manner by acting through master regulatory genes operating in cells with specific microenvironmental interactions. Two of these regulatory genes, fos and jun, are discussed in detail because of their induction by growth factors and their central role in the transactivation of genes which have been implicated in rheumatoid synovitis. A model for gene activation in the rheumatoid synovium is proposed based on the premise that fos and jun are an important link in the intracellular transduction pathways used by cytokines to induce cellular phenotypic changes.

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Immunohistochemical characterization of synovial cells in arthritic mrl‐lpr/lpr mice

Abstract: MRL-lpr/lpr (MRWl

Cited by 38 publications

References 37 publications

Fas-Independent T-Cell Apoptosis by Dendritic Cells Controls Autoimmune Arthritis in MRL/lpr Mice

Fas-Independent T-Cell Apoptosis by Dendritic Cells Controls Autoimmune Arthritis in MRL/lpr Mice

What can we learn about rheumatoid arthritis from animal models?

Potential mechanisms for coordinate gene activation in the rheumatoid synoviocyte: Implications and hypotheses

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