Dermatopathological studies on skin lesions of MRL mice

Furukawa, Fukumi; Tanaka, Hitoshi; Sekita, Kenichi; Nakamura, Toshio; Horiguchi, Yuji; Hamashima, Yoshihiro

doi:10.1007/bf00414018

Cited by 113 publications

(87 citation statements)

References 14 publications

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“…MRL-Fas lpr mice typically develop skin lesions of back, neck, and ears by age 5-6 mo (29,30). To determine whether IL-10 is associated with the development of the skin lesions that characterize MRL-Fas lpr mice, we also blindly analyzed our initial cohort of 47 mice, described in the mortality assessment in Fig.…”

Section: Il-10 Suppresses Skin Lesions In Mrl-fas Lpr Micementioning

confidence: 99%

IL-10 Regulates Murine Lupus

Yin

Bahtiyar

Zhang

et al. 2002

The Journal of Immunology

210

175

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MRL/MpJ-Tnfrsf6lpr (MRL/MpJ-Faslpr; MRL-Faslpr) mice develop a spontaneous lupus syndrome closely resembling human systemic lupus erythematosus. To define the role of IL-10 in the regulation of murine lupus, IL-10 gene-deficient (IL-10−/−) MRL-Faslpr (MRL-Faslpr IL-10−/−) mice were generated and their disease phenotype was compared with littermates with one or two copies of an intact IL-10 locus (MRL-Faslpr IL-10+/− and MRL-Faslpr IL-10+/+ mice, respectively). MRL-Faslpr IL-10−/− mice developed severe lupus, with earlier appearance of skin lesions, increased lymphadenopathy, more severe glomerulonephritis, and higher mortality than their IL-10-intact littermate controls. The increased severity of lupus in MRL-Faslpr IL-10−/− mice was closely associated with enhanced IFN-γ production by both CD4+ and CD8+ cells and increased serum concentration of IgG2a anti-dsDNA autoantibodies. The protective effect of IL-10 in this lupus model was further supported by the observation that administration of rIL-10 reduced IgG2a anti-dsDNA autoantibody production in wild-type MRL-Faslpr animals. In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus.

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Section: Il-10 Suppresses Skin Lesions In Mrl-fas Lpr Micementioning

confidence: 99%

IL-10 Regulates Murine Lupus

Yin

Bahtiyar

Zhang

et al. 2002

The Journal of Immunology

210

175

View full text Add to dashboard Cite

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“…MRL-lpr mice develop inflammatory skin lesions that typically manifest as hair loss and scab formation on the dorsal neck region as well as cellular infiltration and epidermal hyperplasia visible on histology [3,4]. We monitored the development of such skin lesions and scored the skin biopsy sections from dorsal regions of the neck for cellular infiltration, epidermal hyperplasia and epidermal ulcerations.…”

Section: Cd1d Deficiency Exacerbates Inflammatory Skin Lesions In Mrlmentioning

confidence: 99%

“…Inflammatory skin lesions on the forehead, ears and dorsum of the neck [3,4,14] were scored on a scale of 0-3, where 0= no visible skin changes, 1= minimal hair loss with redness and a few scattered lesions, 2= redness, scabbing and hair loss with a small area of involvement and 3= ulcerations with an extensive area of involvement. For histology, skin biopsies from the back of neck were stored in 4% paraformaldehyde and sectioned.…”

Section: Assessment Of Skin Diseasementioning

confidence: 99%

“…MRL-lpr/lpr (MRL-lpr) mice spontaneously develop inflammatory lesions in skin, kidneys and blood vessels, along with marked lymphoproliferation, autoantibody production and hypergammaglobulinemia [1][2][3][4][5][6]. These mice have been widely used as a model to study the pathogenesis of SLE, a multi-organ autoimmune disease [7].…”

Section: Introductionmentioning

confidence: 99%

“…Skin lesions that resemble human discoid lupus erythematosus typically develop on the dorsum of the neck, forehead and ears of MRL-lpr mice. Histology of these lesions reveals epidermal hyperplasia, vacuolar cell changes, cellular infiltration and epidermal ulcerations [3,4]. These lesions markedly worsen in MRL-lpr mice that have been rendered deficient in g 2-microglobulin ( g 2m) [8].…”

Section: Introductionmentioning

confidence: 99%

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CD1d deficiency exacerbates inflammatory dermatitis in MRL‐lpr/lpr mice

et al. 2004

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Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/ lpr mice had increased prevalence of CD4 + T cells in the spleen and liver and of TCR § g + B220 + cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.

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Abrogation of skin disease in LUPUS‐prone MRL/FAS^lpr mice by means of a novel tylophorine analog

Choi¹,

Gao²,

Odegard³

et al. 2006

Arthritis & Rheumatism

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Objective. To test the therapeutic effect of DCB-3503, a synthetic compound derived from a natural product that inhibits NF-B, on end-organ disease in the MRL-Fas lpr murine model of systemic lupus erythematosus (SLE).Methods. Eight-week-old female MRL/Fas lpr mice were treated intraperitoneally with a low (2 mg/kg) or high (6 mg/kg) dose of DCB-3503 for 10 weeks. Control groups were administered vehicle treatment alone (negative control) or 25 mg/kg cyclophosphamide (positive control). Mice were bled before (8 weeks) and during (13 weeks) treatment, and when they were killed (20 weeks), and serum samples were analyzed for total IgM and IgG levels and autoantibody titers. When the mice were killed, spleen and lymph nodes (axillary, brachial, and cervical) were examined by flow cytometric analysis. The presence of skin and renal disease was determined by histopathologic analysis.Results. DCB-3503 reduced anti-double-stranded DNA and antichromatin autoantibodies and nearly abrogated inflammatory skin disease in MRL/Fas lpr mice; however, it had little effect on histologic kidney disease. Treated mice did not have hematologic or hepatic toxicity. These data indicate that end-organ disease in MRL/Fas lpr mice responds differentially to NF-B inhibitor.Conclusion. DCB-3503 causes significant abrogation of skin disease in MRL/Fas lpr mice and may potentially be beneficial in the treatment of inflammatory skin disease in SLE.

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Dermatopathological studies on skin lesions of MRL mice

Cited by 113 publications

References 14 publications

IL-10 Regulates Murine Lupus

IL-10 Regulates Murine Lupus

CD1d deficiency exacerbates inflammatory dermatitis in MRL‐lpr/lpr mice

Abrogation of skin disease in LUPUS‐prone MRL/FAS^lpr mice by means of a novel tylophorine analog

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Dermatopathological studies on skin lesions of MRL mice

Cited by 113 publications

References 14 publications

IL-10 Regulates Murine Lupus

IL-10 Regulates Murine Lupus

CD1d deficiency exacerbates inflammatory dermatitis in MRL‐lpr/lpr mice

Abrogation of skin disease in LUPUS‐prone MRL/FASlpr mice by means of a novel tylophorine analog

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Abrogation of skin disease in LUPUS‐prone MRL/FAS^lpr mice by means of a novel tylophorine analog