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

Izawa, Takashi; Kondo, Takao; Kurosawa, Mie; Oura, Ritsuko; Matsumoto, K; Tanaka, Eiji; Yamada, Akiko; Arakaki, Rieko; Kudo, Yasusei; Hayashi, Yoshio; Ishimaru, Naozumi

doi:10.1371/journal.pone.0048798

Cited by 18 publications

(14 citation statements)

References 53 publications

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“…Indeed, astilbin decreased the mitochondrial membrane potential in activated T cells from naïve MRL/lpr mice, supported by an increase in the green fluorescence of JC-1. A recent study has also indicated that Fas-independent T-cell apoptosis maintains peripheral tolerance and thus controls autoimmune arthritis in MRL/lpr mice [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Decrease of Functional Activated T and B Cells and Treatment of Glomerulonephitis in Lupus-Prone Mice Using a Natural Flavonoid Astilbin

Guo

et al. 2015

PLoS ONE

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Treatment of systemic lupus erythematosus (SLE), a chronic inflammatory disease, involves the long-term use of immunosuppressive agents with significant side effects. New therapeutic approaches are being explored to find better treatment possibilities. In this study, age-matched female MRL/lpr mice were treated orally with a natural flavonoid astilbin. Astilbin administration started either at week 8 or week 12 of age though week 20. In the early treatment regimen, the treatment with astilbin reduced splenomegaly / lymphomegaly, autoantibody production and ameliorated lupus nephitis. Several serum cytokines were significantly decreased upon treatment including IFN-g, IL-17A, IL-1b, TNF-a and IL-6. Both spleen CD44hiCD62Llo activated T cells and CD138+B220- plasma cells greatly declined. Furthermore, astilbin treatment resulted in decreased mitochondrial membrane potential in activated T cells and downregulated expression of the co-stimulatory molecules CD80 and CD86 on LPS stimulated B cells. Similar but less profound effectiveness was observed in the mice with established disease in the late treatment regimen. These results indicate that the natural product astilbin can mitigate disease development in lupus-prone mice by decreasing functional activated T and B cells.

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Section: Discussionmentioning

confidence: 99%

Decrease of Functional Activated T and B Cells and Treatment of Glomerulonephitis in Lupus-Prone Mice Using a Natural Flavonoid Astilbin

Guo

et al. 2015

PLoS ONE

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“…More than half of the T cells were already apoptotic (Anexin V+PI−) in the absence of treatment with resveratrol in our study, which is related to the culture duration of up to 36 h in vitro . Indeed, it is known that the viability of T cells decreases as culture duration is prolonged [25] , [26] . In addition, resveratrol can inhibit the antibody production and proliferation of B cells in vitro , which is consistent with previous reports [27] .…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Possesses Protective Effects in a Pristane-Induced Lupus Mouse Model

Wang

Luo

et al. 2014

PLoS ONE

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BackgroundSystemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by the production of autoantibodies. To date, no therapy has been found to satisfactorily treat SLE. SIRT1 deficiency results in the development of an autoimmune syndrome in mice, including a high titer of anti-nuclear antibody in serum, immunoglobulin deposition in the kidney, and immune complex glomerulonephritis. Resveratrol is an activator of SIRT1 and possesses anti-inflammation and immune-regulatory properties.ObjectiveTo evaluate the preventative effects of resveratrol on a pristane-induced lupus animal model and assess its putative immune modulation effects.MethodsBALB/c mice received a single intraperitoneal injection of 0.5 ml of pristane on day 1 and then various doses of resveratrol were given to the mice daily starting on day 2 and continuing for seven months. The autoantibodies in serum and supernatants were measured. Single cells isolated from spleen, isolated CD4+ T cells, and CD19+ B cells were cultured with or without resveratrol in vitro and assessed by flow cytometry.ResultsResveratrol attenuated proteinuria, immunoglobuin depositon in kidney, and glomerulonephritis as well as IgG1 and IgG2a in serum in pristane-induced lupus mice. Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro. In vitro antibody production and proliferation of B cells were also inhibited.ConclusionResveratrol possesses protective effects in pristane-induced lupus mice and may represent a novel approach for the management of SLE.

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“…Evidence indicates that autoreactive T cells are abundant in the periphery of lpr/lpr or gld/gld mice as well as in patients with ALPS (10, 11, 19, 20). By contrast, Fas-independent T cell apoptosis is induced by the direct interaction between TRAIL-R2 on T cells and TRAIL on Fas-deficient dendritic cells in MRL- lpr/lpr mice (42). Thus, member of the TNFR family, including Fas and TRAIL-R2, likely play a key role in the maintenance of peripheral immune tolerance.…”

Section: Fas-mediated T Cell Immune Regulationmentioning

confidence: 99%

Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance

et al. 2017

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Fas-mediated apoptosis contributes to physiological and pathological cellular processes, such as differentiation and survival. In particular, the roles of Fas in immune cells are complex and critical for the maintenance of immune tolerance. The precise pathways and unique functions associated with Fas/FasL-mediated signaling in the immune system are known. The dual character of Fas/FasL-mediated immune regulation that induces beneficial or harmful effects is associated with the onset or development of immune disorders. Studies on mutations in genes encoding Fas and FasL gene of humans and mice contributed to our understanding of the pathogenesis of autoimmune diseases. Here, we review the opposing functions of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells, and complex pathogenesis of autoimmunity mediated by Fas/FasL.

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

Cited by 18 publications

References 53 publications

Decrease of Functional Activated T and B Cells and Treatment of Glomerulonephitis in Lupus-Prone Mice Using a Natural Flavonoid Astilbin

Decrease of Functional Activated T and B Cells and Treatment of Glomerulonephitis in Lupus-Prone Mice Using a Natural Flavonoid Astilbin

Resveratrol Possesses Protective Effects in a Pristane-Induced Lupus Mouse Model

Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance

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